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Neag G, Lewis J, Turner JD, Manning JE, Dean I, Finlay M, Poologasundarampillai G, Woods J, Sahu MA, Khan KA, Begum J, McGettrick HM, Bellantuono I, Heath V, Jones SW, Buckley CD, Bicknell R, Naylor AJ. Type-H endothelial cell protein Clec14a orchestrates osteoblast activity during trabecular bone formation and patterning. Commun Biol 2024; 7:1296. [PMID: 39394430 PMCID: PMC11470016 DOI: 10.1038/s42003-024-06971-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 09/26/2024] [Indexed: 10/13/2024] Open
Abstract
Type-H capillary endothelial cells control bone formation during embryogenesis and postnatal growth but few signalling mechanisms underpinning this influence have been characterised. Here, we identify a highly expressed type-H endothelial cell protein, Clec14a, and explore its role in coordinating osteoblast activity. Expression of Clec14a and its ligand, Mmrn2 are high in murine type-H endothelial cells but absent from osteoblasts. Clec14a-/- mice have premature condensation of the type-H vasculature and expanded distribution of osteoblasts and bone matrix, increased long-bone length and bone density indicative of accelerated skeletal development, and enhanced osteoblast maturation. Antibody-mediated blockade of the Clec14a-Mmrn2 interaction recapitulates the Clec14a-/- phenotype. Endothelial cell expression of Clec14a regulates osteoblast maturation and mineralisation activity during postnatal bone development in mice. This finding underscores the importance of type-H capillary control of osteoblast activity in bone formation and identifies a novel mechanism that mediates this vital cellular crosstalk.
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Affiliation(s)
- Georgiana Neag
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Jonathan Lewis
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Jason D Turner
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Julia E Manning
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Isaac Dean
- School of Medical Sciences, University of Birmingham, Birmingham, UK
| | - Melissa Finlay
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | | | - Jonathan Woods
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Muhammad Arham Sahu
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Kabir A Khan
- School of Medical Sciences, University of Birmingham, Birmingham, UK
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada
| | - Jenefa Begum
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Helen M McGettrick
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Ilaria Bellantuono
- Healthy Lifespan Institute, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Victoria Heath
- School of Medical Sciences, University of Birmingham, Birmingham, UK
| | - Simon W Jones
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
| | - Christopher D Buckley
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK
- The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
| | - Roy Bicknell
- School of Medical Sciences, University of Birmingham, Birmingham, UK
| | - Amy J Naylor
- Rheumatology Research Group, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
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Solorzano E, Alejo AL, Ball HC, Robinson GT, Solorzano AL, Safadi R, Douglas J, Kelly M, Safadi FF. The Lymphatic Endothelial Cell Secretome Inhibits Osteoblast Differentiation and Bone Formation. Cells 2023; 12:2482. [PMID: 37887326 PMCID: PMC10605748 DOI: 10.3390/cells12202482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 09/15/2023] [Accepted: 09/18/2023] [Indexed: 10/28/2023] Open
Abstract
Complex lymphatic anomalies (CLAs) are a set of rare diseases with unique osteopathic profiles. Recent efforts have identified how lymphatic-specific somatic activating mutations can induce abnormal lymphatic formations that are capable of invading bone and inducing bone resorption. The abnormal bone resorption in CLA patients has been linked to overactive osteoclasts in areas with lymphatic invasions. Despite these findings, the mechanism associated with progressive bone loss in CLAs remains to be elucidated. In order to determine the role of osteoblasts in CLAs, we sought to assess osteoblast differentiation and bone formation when exposed to the lymphatic endothelial cell secretome. When treated with lymphatic endothelial cell conditioned medium (L-CM), osteoblasts exhibited a significant decrease in proliferation, differentiation, and function. Additionally, L-CM treatment also inhibited bone formation through a neonatal calvaria explant culture. These findings are the first to reveal how osteoblasts may be actively suppressed during bone lymphatic invasion in CLAs.
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Affiliation(s)
- Ernesto Solorzano
- Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA; (E.S.); (A.L.A.); (H.C.B.); (G.T.R.); (A.L.S.)
- Musculoskeletal Research Group, NEOMED, Rootstown, OH 44272, USA;
- Basic and Translational Biomedicine (BTB) Graduate Program, College of Graduate Studies, NEOMED, Rootstown, OH 44272, USA;
| | - Andrew L. Alejo
- Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA; (E.S.); (A.L.A.); (H.C.B.); (G.T.R.); (A.L.S.)
| | - Hope C. Ball
- Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA; (E.S.); (A.L.A.); (H.C.B.); (G.T.R.); (A.L.S.)
- Musculoskeletal Research Group, NEOMED, Rootstown, OH 44272, USA;
- Basic and Translational Biomedicine (BTB) Graduate Program, College of Graduate Studies, NEOMED, Rootstown, OH 44272, USA;
| | - Gabrielle T. Robinson
- Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA; (E.S.); (A.L.A.); (H.C.B.); (G.T.R.); (A.L.S.)
- Musculoskeletal Research Group, NEOMED, Rootstown, OH 44272, USA;
- Basic and Translational Biomedicine (BTB) Graduate Program, College of Graduate Studies, NEOMED, Rootstown, OH 44272, USA;
| | - Andrea L. Solorzano
- Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA; (E.S.); (A.L.A.); (H.C.B.); (G.T.R.); (A.L.S.)
| | - Rama Safadi
- College of Arts and Sciences, Kent State University, Kent, OH 44243, USA;
| | - Jacob Douglas
- Musculoskeletal Research Group, NEOMED, Rootstown, OH 44272, USA;
| | - Michael Kelly
- Basic and Translational Biomedicine (BTB) Graduate Program, College of Graduate Studies, NEOMED, Rootstown, OH 44272, USA;
- Department of Pediatric Hematology Oncology and Blood, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Fayez F. Safadi
- Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, OH 44272, USA; (E.S.); (A.L.A.); (H.C.B.); (G.T.R.); (A.L.S.)
- Musculoskeletal Research Group, NEOMED, Rootstown, OH 44272, USA;
- Basic and Translational Biomedicine (BTB) Graduate Program, College of Graduate Studies, NEOMED, Rootstown, OH 44272, USA;
- Rebecca D. Considine Research Institute, Akron Children’s Hospital, Akron, OH 44308, USA
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Hanetseder D, Levstek T, Teuschl-Woller AH, Frank JK, Schaedl B, Redl H, Marolt Presen D. Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age. Front Bioeng Biotechnol 2023; 11:1214019. [PMID: 37600321 PMCID: PMC10434254 DOI: 10.3389/fbioe.2023.1214019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 07/10/2023] [Indexed: 08/22/2023] Open
Abstract
Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing.
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Affiliation(s)
- Dominik Hanetseder
- Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Tina Levstek
- Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Andreas Herbert Teuschl-Woller
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- Department Life Science Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria
| | - Julia Katharina Frank
- Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Barbara Schaedl
- Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Heinz Redl
- Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Darja Marolt Presen
- Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation with AUVA, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
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Yuan W, Hu Y, Lu C, Zhang J, Liu Y, Li X, Jia K, Huang Y, Li Z, Chen X, Wang F, Yi X, Che X, Xiong H, Cheng B, Ma J, Zhao Y, Lu H. Propineb induced notochord deformity, craniofacial malformation, and osteoporosis in zebrafish through dysregulated reactive oxygen species generation. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2023; 261:106596. [PMID: 37290275 DOI: 10.1016/j.aquatox.2023.106596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/28/2023] [Accepted: 05/30/2023] [Indexed: 06/10/2023]
Abstract
Dithiocarbamate (DTC) fungicides are contaminants that are ubiquitous in the environment. Exposure to DTC fungicides has been associated with a variety of teratogenic developmental effects. Propineb, a member of DTCs, was evaluated for the toxicological effects on notochord and craniofacial development, osteogenesis in zebrafish model. Embryos at 6 hours post-fertilization (hpf) were exposed to propineb at dosages of 1 and 4 μM. Morphological parameters were evaluated at exposure times of 24, 48, 72, and 120 hpf after propineb exposure. The survival and hatching rates as well as body length decreased at 1 and 4 μmol/L groups. Besides, transgenic zebrafish exposed to propineb showed abnormal vacuole biogenesis in notochord cells at the early stage of development. The expression of collagen type 2 alpha 1a (col2a1a), sonic hedgehog (shh), and heat shock protein family B member 11 (hspb11) measured by quantitative PCR and in situ hybridization experiment of col8a1a gene have consolidated the proposal process. Besides, Alcian blue, calcein, and alizarin red staining profiles displayed craniofacial malformations and osteoporosis were induced following propineb exposure. PPB exposure induced the changes in oxidative stress and reactive oxygen species inhibitor alleviated the deformities of PPB. Collectively, our data suggested that propineb exposure triggered bone abnormalities in different phenotypes of zebrafish. Therefore, propineb is a potential toxicant of high priority concern for aquatic organisms.
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Affiliation(s)
- Wei Yuan
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Ying Hu
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Chen Lu
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Jun Zhang
- Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment of the People's Republic of China, Nanjing, 210042, Jiangsu, China
| | - Ye Liu
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Xinran Li
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Kun Jia
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Yong Huang
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Zekun Li
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Xiaomei Chen
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Fei Wang
- The First Clinical College of Gannan Medical Uinversity, Ganzhou, 341000, Jiangxi, China
| | - Xiaokun Yi
- The First Clinical College of Gannan Medical Uinversity, Ganzhou, 341000, Jiangxi, China
| | - Xiaofang Che
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Haibin Xiong
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Bo Cheng
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Jinze Ma
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Yan Zhao
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China
| | - Huiqiang Lu
- Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000, Jiangxi, China; Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, Jiangxi, China..
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Franceschi RT, Hallett SA, Ge C. Discoidin domain receptors; an ancient family of collagen receptors has major roles in bone development, regeneration and metabolism. FRONTIERS IN DENTAL MEDICINE 2023; 4:1181817. [PMID: 38222874 PMCID: PMC10785288 DOI: 10.3389/fdmed.2023.1181817] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2024] Open
Abstract
The extracellular matrix (ECM) niche plays a critical role in determining cellular behavior during bone development including the differentiation and lineage allocation of skeletal progenitor cells to chondrocytes, osteoblasts, or marrow adipocytes. As the major ECM component in mineralized tissues, collagen has instructive as well as structural roles during bone development and is required for bone cell differentiation. Cells sense their extracellular environment using specific cell surface receptors. For many years, specific β1 integrins were considered the main collagen receptors in bone, but, more recently, the important role of a second, more primordial collagen receptor family, the discoidin domain receptors, has become apparent. This review will specifically focus on the roles of discoidin domain receptors in mineralized tissue development as well as related functions in abnormal bone formation, regeneration and metabolism.
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Affiliation(s)
- Renny T. Franceschi
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States
| | - Shawn A. Hallett
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States
| | - Chunxi Ge
- Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, United States
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Rizzo MG, Palermo N, Alibrandi P, Sciuto EL, Del Gaudio C, Filardi V, Fazio B, Caccamo A, Oddo S, Calabrese G, Conoci S. Physiologic Response Evaluation of Human Foetal Osteoblast Cells within Engineered 3D-Printed Polylactic Acid Scaffolds. BIOLOGY 2023; 12:biology12030424. [PMID: 36979116 PMCID: PMC10044883 DOI: 10.3390/biology12030424] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/07/2023] [Accepted: 03/09/2023] [Indexed: 03/12/2023]
Abstract
Large bone defect treatments have always been one of the important challenges in clinical practice and created a huge demand for more efficacious regenerative approaches. The bone tissue engineering (BTE) approach offered a new alternative to conventional bone grafts, addressing all clinical needs. Over the past years, BTE research is focused on the study and realisation of new biomaterials, including 3D-printed supports to improve mechanical, structural and biological properties. Among these, polylactic acid (PLA) scaffolds have been considered the most promising biomaterials due to their good biocompatibility, non-toxic biodegradability and bioresorbability. In this work, we evaluated the physiological response of human foetal osteoblast cells (hFOB), in terms of cell proliferation and osteogenic differentiation, within oxygen plasma treated 3D-printed PLA scaffolds, obtained by fused deposition modelling (FDM). A mechanical simulation to predict their behaviour to traction, flexural or torque solicitations was performed. We found that: 1. hFOB cells adhere and grow on scaffold surfaces; 2. hFOB grown on oxygen plasma treated PLA scaffolds (PLA_PT) show an improvement of cell adhesion and proliferation, compared to not-plasma treated scaffolds (PLA_NT); 3. Over time, hFOB penetrate along strands, differentiate, and form a fibrous matrix, tissue-like; 4. 3D-printed PLA scaffolds have good mechanical behaviour in each analysed configuration. These findings suggest that 3D-printed PLA scaffolds could represent promising biomaterials for medical implantable devices in the orthopaedic field.
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Affiliation(s)
- Maria Giovanna Rizzo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
| | - Nicoletta Palermo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
| | - Paola Alibrandi
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
| | - Emanuele Luigi Sciuto
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
| | | | | | - Barbara Fazio
- CNR URT Lab SENS, Beyond NANO, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
- CNR-IPCF, Istituto per i Processi Chimico-Fisici, Viale F. Stagno D’Alcontres 37, 98158 Messina, Italy
| | - Antonella Caccamo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
| | - Salvatore Oddo
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
| | - Giovanna Calabrese
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
- Correspondence: (G.C.); (S.C.)
| | - Sabrina Conoci
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98168 Messina, Italy
- CNR URT Lab SENS, Beyond NANO, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy
- Correspondence: (G.C.); (S.C.)
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Lu T, Yan S, Shi H, Ye J. Synthesis, Characterization, In Vitro Cytological Responses, and In Vivo Bone Regeneration Effects of Low-Crystalline Nanocarbonated Hydroxyapatite. ACS Biomater Sci Eng 2023; 9:918-931. [PMID: 36700921 DOI: 10.1021/acsbiomaterials.2c01272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Hydroxyapatite (HA) has been commonly used as an alternative bone substitute. But it has drawbacks, such as poor degradation and limited osteogenesis. Low-crystalline carbonated hydroxyapatite (L-CHA), which has greater biodegradability than HA, is suggested as one of the main components of bone minerals, but the exact mechanism behind the roles of carbonate substituted in biological behaviors of low-crystalline HA is still a mystery. In this study, L-CHAs with different carbonate contents were prepared, and the effects of the content on the physicochemical properties, in vitro cytological responses, and in vivo bone defects repair effects of L-CHAs were investigated. The results demonstrated that CO32- had successfully entered the lattice structure of L-CHAs with a maximum content of 9.2 wt %. Both low-crystalline undoped HA (L-HA) and L-CHAs were nanocrystalline (20-30 nm) with significantly higher specific surface areas, protein adsorption capacities, and biodegradability compared to high-crystalline HA (H-HA) with submicron crystalline size (200-400 nm). Besides, the amounts of the adsorbed protein and released Ca2+ ions increased in a carbonate-content-dependent manner. Compared to L-HA and H-HA, L-CHAs promoted the adhesion and proliferation of bone marrow mesenchymal stem cells and significantly upregulated the levels of alkaline phosphatase (ALP) activity and the expression of osteogenesis-related genes. In addition, L-CHA-9 not only showed a faster biodegradation rate but also effectively promoted bone regeneration when implanted in the critical-sized bone defects of rabbit femora. This study provided evidence for the development of L-CHA as a promising biodegradable and bioactive material with great osteoconductivity and osteogenic capability with respect to conventional HA.
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Affiliation(s)
- Teliang Lu
- School of Materials Science and Engineering, South China University of Technology, Guangzhou510641, P. R. China.,National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou510006, P. R. China
| | - Siwen Yan
- School of Materials Science and Engineering, South China University of Technology, Guangzhou510641, P. R. China.,National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou510006, P. R. China
| | - Haishan Shi
- School of Stomatology, Jinan University, Guangzhou510632, P. R. China
| | - Jiandong Ye
- School of Materials Science and Engineering, South China University of Technology, Guangzhou510641, P. R. China.,National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou510006, P. R. China.,Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou510006, P. R. China
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8
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Suitability of R. pulmo Jellyfish-Collagen-Coated Well Plates for Cytocompatibility Analyses of Biomaterials. Int J Mol Sci 2023; 24:ijms24033007. [PMID: 36769326 PMCID: PMC9917789 DOI: 10.3390/ijms24033007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 01/27/2023] [Accepted: 02/01/2023] [Indexed: 02/05/2023] Open
Abstract
Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/-12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.
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9
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Fan L, Körte F, Rudt A, Jung O, Burkhardt C, Barbeck M, Xiong X. Encapsulated vaterite-calcite CaCO 3 particles loaded with Mg 2+ and Cu 2+ ions with sustained release promoting osteogenesis and angiogenesis. Front Bioeng Biotechnol 2022; 10:983988. [PMID: 36032705 PMCID: PMC9403055 DOI: 10.3389/fbioe.2022.983988] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 07/18/2022] [Indexed: 11/13/2022] Open
Abstract
Bioactive cations, including calcium, copper and magnesium, have shown the potential to become the alternative to protein growth factor-based therapeutics for bone healing. Ion substitutions are less costly, more stable, and more effective at low concentrations. Although they have been shown to be effective in providing bone grafts with more biological functions, the precise control of ion release kinetics is still a challenge. Moreover, the synergistic effect of three or more metal ions on bone regeneration has rarely been studied. In this study, vaterite-calcite CaCO3 particles were loaded with copper (Cu2+) and magnesium (Mg2+). The polyelectrolyte multilayer (PEM) was deposited on CaCuMg-CO3 particles via layer-by-layer technique to further improve the stability and biocompatibility of the particles and to enable controlled release of multiple metal ions. The PEM coated microcapsules were successfully combined with collagen at the outmost layer, providing a further stimulating microenvironment for bone regeneration. The in vitro release studies showed remarkably stable release of Cu2+ in 2 months without initial burst release. Mg2+ was released in relatively low concentration in the first 7 days. Cell culture studies showed that CaCuMg-PEM-Col microcapsules stimulated cell proliferation, extracellular maturation and mineralization more effectively than blank control and other microcapsules without collagen adsorption (Ca-PEM, CaCu-PEM, CaMg-PEM, CaCuMg-PEM). In addition, the CaCuMg-PEM-Col microcapsules showed positive effects on osteogenesis and angiogenesis in gene expression studies. The results indicate that such a functional and controllable delivery system of multiple bioactive ions might be a safer, simpler and more efficient alternative of protein growth factor-based therapeutics for bone regeneration. It also provides an effective method for functionalizing bone grafts for bone tissue engineering.
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Affiliation(s)
- Lu Fan
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
- Experimental Medicine, Faculty of Medicine, University of Tübingen, Tübingen, Germany
| | - Fabian Körte
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
| | - Alexander Rudt
- Faculty of Applied Chemistry, Reutlingen University, Reutlingen, Germany
| | - Ole Jung
- Medical Center of Rostock University, Rostock, Germany
| | - Claus Burkhardt
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
| | - Mike Barbeck
- Medical Center of Rostock University, Rostock, Germany
| | - Xin Xiong
- NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany
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10
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Yu X, Wang J, Han Q, Chu W, Lu S, Liu Y, Peng Y, Xu J, Shui Y. Effects of Yunnan Baiyao on the Differentiation of HPDLFs on the Bio-Oss® Collagen Scaffold in vivo. Int J Gen Med 2022; 15:5395-5405. [PMID: 35685694 PMCID: PMC9173728 DOI: 10.2147/ijgm.s359921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 05/09/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Xiaohong Yu
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Jing Wang
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Qianqian Han
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Wen Chu
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Shaowen Lu
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Yu Liu
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Yi Peng
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Jie Xu
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
| | - Yanqing Shui
- Department of Periodontology, School and Hospital of Stomatology, Kunming Medical University, Yunnan, People’s Republic of China
- Correspondence: Yanqing Shui, Department of Periodontology, Affiliated Stomatology Hospital of Kunming Medical University, Block C, Hecheng International, No. 1088 Haiyuan Middle Road, Wuhua District, Kunming, 650106, Yunnan, People’s Republic of China, Tel +86 15987150210, Email
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11
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Aizawa H, Uematsu T, Sato A, Masuki H, Kawabata H, Tsujino T, Isobe K, Kitamura Y, Nagata M, Nakata K, Kawase T. Non-destructive, spectrophotometric analysis of the thickness of the cell-multilayered periosteal sheet. Int J Implant Dent 2022; 8:21. [PMID: 35491414 PMCID: PMC9058046 DOI: 10.1186/s40729-022-00419-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 04/08/2022] [Indexed: 11/22/2022] Open
Abstract
Background Autologous tissue-engineered periosteal sheets, which have been clinically applied for periodontal regeneration, sinus lift, and alveolar ridge augmentation, are enriched with osteoblast precursor cells and the abundant deposition of collagen type I in the extracellular spaces. Their quality is inspected prior to clinical use; however, most criteria cannot be evaluated without sacrificing samples. To reduce such losses, we developed a non-destructive optical method that can quantitatively evaluate the thickness of the periosteal sheet. Methods Dispersed periosteal cells were inoculated into small pieces of collagen sponge (Terudermis®) and plated into 60-mm dishes for further explant culture using a conventional medium and a stem-cell culture medium. The thickness of periosteal sheets was evaluated using inverted microscopic, histological, labeling (CellVue®)-based imaging and spectrophotometric (Spectro-1®) methods. Results The three-dimensional growth of periosteal sheets did not necessarily correlate with two-dimensional growth. The periosteal sheet prepared with the stem-cell medium formed cell multilayers, a phenomenon that could be observed qualitatively by inverted microscopy. The spectrophotometric analysis enabled the quantitative evaluation of the thickness of the cell multilayer without sacrificing the samples processed for scheduled cell therapy. Conclusions The growth of periosteal sheets is influenced by several major factors, including the basic quality of the individual original periosteal tissue segments, the technical expertise of doctors and operators involved in tissue harvesting and processing, and culture conditions. This newly developed spectrophotometric analysis can quantify the thickness of cell-multilayered periosteal sheets for quality assurance in a non-destructive manner, thereby contributing to better bone augmentation prior to implant therapy.
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12
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Chen Y, Yang S, Lovisa S, Ambrose CG, McAndrews KM, Sugimoto H, Kalluri R. Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta. Nat Commun 2021; 12:7199. [PMID: 34893625 PMCID: PMC8664945 DOI: 10.1038/s41467-021-27563-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 11/16/2021] [Indexed: 01/15/2023] Open
Abstract
Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap+ cells and Fsp1+ cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap+ cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1+ cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta.
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Affiliation(s)
- Yang Chen
- grid.240145.60000 0001 2291 4776Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 USA
| | - Sujuan Yang
- grid.240145.60000 0001 2291 4776Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 USA
| | - Sara Lovisa
- grid.240145.60000 0001 2291 4776Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 USA
| | - Catherine G. Ambrose
- grid.267308.80000 0000 9206 2401Department of Orthopaedic Surgery, University of Texas Health Science Center at Houston, Houston, TX USA
| | - Kathleen M. McAndrews
- grid.240145.60000 0001 2291 4776Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 USA
| | - Hikaru Sugimoto
- grid.240145.60000 0001 2291 4776Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 USA
| | - Raghu Kalluri
- Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA. .,Department of Bioengineering, Rice University, Houston, TX, USA. .,Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
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13
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Functionalization of Electrospun Polycaprolactone Scaffolds with Matrix-Binding Osteocyte-Derived Extracellular Vesicles Promotes Osteoblastic Differentiation and Mineralization. Ann Biomed Eng 2021; 49:3621-3635. [PMID: 34664147 PMCID: PMC8671272 DOI: 10.1007/s10439-021-02872-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 09/28/2021] [Indexed: 12/14/2022]
Abstract
Synthetic polymeric materials have demonstrated great promise for bone tissue engineering based on their compatibility with a wide array of scaffold-manufacturing techniques, but are limited in terms of the bioactivity when compared to naturally occurring materials. To enhance the regenerative properties of these materials, they are commonly functionalised with bioactive factors to guide growth within the developing tissue. Extracellular matrix vesicles (EVs) play an important role in facilitating endochondral ossification during long bone development and have recently emerged as important mediators of cell-cell communication coordinating bone regeneration, and thus represent an ideal target to enhance the regenerative properties of synthetic scaffolds. Therefore, in this paper we developed tools and protocols to enable the attachment of MLO-Y4 osteocyte-derived EVs onto electrospun polycaprolactone (PCL) scaffolds for bone repair. Initially, we optimize a method for the functionalization of PCL materials with collagen type-1 and fibronectin, inspired by the behaviour of matrix vesicles during endochondral ossification, and demonstrate that this is an effective method for the adhesion of EVs to the material surface. We then used this functionalization process to attach osteogenic EVs, collected from mechanically stimulated MLO-Y4 osteocytes, to collagen-coated electrospun PCL scaffolds. The EV-functionalized scaffold promoted osteogenic differentiation (measured by increased ALP activity) and mineralization of the matrix. In particular, EV-functionalised scaffolds exhibited significant increases in matrix mineralization particularly at earlier time points compared to uncoated and collagen-coated controls. This approach to matrix-based adhesion of EVs provides a mechanism for incorporating vesicle signalling into polyester scaffolds and demonstrates the potential of osteocyte derived EVs to enhance the rate of bone tissue regeneration.
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14
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Shen K, Zhang X, Tang Q, Fang X, Zhang C, Zhu Z, Hou Y, Lai M. Microstructured titanium functionalized by naringin inserted multilayers for promoting osteogenesis and inhibiting osteoclastogenesis. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2021; 32:1865-1881. [PMID: 34233132 DOI: 10.1080/09205063.2021.1949098] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Osteoporosis is the most common cause of fractures in middle-aged and elderly people. Fracture repair can be difficult due to the decreased bone volume in osteoporosis patients and implants are often required. In this study, a slow-release system for microstructured titanium (Micro-Ti) was designed to promote osteogenesis and inhibit osteoclastogenesis. Firstly, Micro-Ti was prepared on titanium surfaces by dual acid etching. Micro-Ti was covered with naringin (NA), chitosan (CHI) and gelatin (GEL) multilayers through layer by layer technique, which is denoted as LBL (NA) coated-Ti. Osteoblasts (ME3T3-E1) and macrophages (RAW 264.7) were cultured on untreated and treated titanium surfaces in vitro. Osteoblasts grown on LBL (NA) coated-Ti showed higher alkaline phosphatase (ALP) and mineralization, consistent with qRT-PCR analysis of osteoblast genes including runt-related transcription factor 2 (Runx2), ALP, collagen I (Col I), osteocalcin (OCN), osteopontin (OPN), and osteoprotegerin (OPG). In contrast, acid tartarate-resistant phosphatase activity and the expression of osteoclastic differentiation related genes comprising of cathepsin K (CTSK), nuclear factor of activated T cells (NFAT), tartrate resistant acid phosphatase (TRAP) and V-ATPase (VATP) in osteoclasts were significantly reduced on LBL (NA) coated-Ti surfaces compared with other groups. These results indicate that microstructured titanium functionalized by naringin inserted multilayers enhanced the differentiation of osteoblasts and inhibited osteoclast formation. The proposed approach in this research provides a novel way to modify titanium-based implants for fracture repair in osteoporosis patients.
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Affiliation(s)
- Ke Shen
- School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
| | - Xiaojing Zhang
- School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
| | - Qiang Tang
- School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
| | - Xingtang Fang
- School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
| | - Chunlei Zhang
- School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
| | - Zhaojing Zhu
- Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing, China
| | - Yanhua Hou
- Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing, China
| | - Min Lai
- School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China
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15
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ElHawary H, Baradaran A, Abi-Rafeh J, Vorstenbosch J, Xu L, Efanov JI. Bone Healing and Inflammation: Principles of Fracture and Repair. Semin Plast Surg 2021; 35:198-203. [PMID: 34526868 PMCID: PMC8432998 DOI: 10.1055/s-0041-1732334] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Bones comprise a significant percentage of human weight and have important physiologic and structural roles. Bone remodeling occurs when healthy bone is renewed to maintain bone strength and maintain calcium and phosphate homeostasis. It proceeds through four phases: (1) cell activation, (2) resorption, (3) reversal, and (4) bone formation. Bone healing, on the other hand, involves rebuilding bone following a fracture. There are two main types of bone healing, primary and secondary. Inflammation plays an integral role in both bone remodeling and healing. Therefore, a tightly regulated inflammatory response helps achieve these two processes, and levels of inflammation can have detrimental effects on bone healing. Other factors that significantly affect bone healing are inadequate blood supply, biomechanical instability, immunosuppression, and smoking. By understanding the different mechanisms of bone healing and the factors that affect them, we may have a better understanding of the underlying principles of bony fixation and thereby improve patient care.
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Affiliation(s)
- Hassan ElHawary
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Aslan Baradaran
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Jad Abi-Rafeh
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Joshua Vorstenbosch
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Liqin Xu
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Johnny Ionut Efanov
- Division of Plastic and Reconstructive Surgery, Centre Hospitalier de l'Université de Montréal, Quebec, Canada
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16
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Azizipour E, Aghamollaei H, Halabian R, Poormoghadam D, Saffari M, Entezari M, Salimi A. A novel hydrogel scaffold contained bioactive glass nanowhisker (BGnW) for osteogenic differentiation of human mesenchymal stem cells (hMSCs) in vitro. Int J Biol Macromol 2021; 174:562-572. [PMID: 33434552 DOI: 10.1016/j.ijbiomac.2021.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/26/2020] [Accepted: 01/01/2021] [Indexed: 12/18/2022]
Abstract
Employing hydrogels as an alternative strategy for repairing bone defects has received great attention in bone tissue engineering. In this study, hydrogel scaffold based on collagen, gelatin, and glutaraldehyde was combined with bioactive glass nanowhiskers (BGnW) to differentiate human mesenchymal stem cells (hMSCs) into the osteogenic lineage and inducing biomineralization. Pure Gel-Glu-Col and bioactive glass nanowhiskers were used as control throughout the paper. Chemical, physical and morphological characteristics of the nanocomposite scaffold were assessed meticulously using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), porosity measurement, water uptake ability, tensile test, and scanning electron microscopy (SEM). To determine the cytotoxicity and cell viability of the hydrogel, MTT assay and Acridine orange (AO) staining were performed. hMSCs seeded on Gel-Glu-Col/BGnW were then incubated with osteogenic differentiation media for 14 days. Biomineralization assays (alkaline phosphatase (ALP) activity, calcium content assay, von Kossa, and Alizarin red staining) were carried out, and osteogenic genes and protein markers were examined using real time-PCR and immunocytochemistry. Results showed that the components of the hydrogel were properly integrated. The mechanical property of hydrogel was enhanced following the addition of BGnW. Cell viability assays confirmed the biocompatibility of the scaffold and increasing the proliferation after incorporating BGnW into pure Ge1-Glu-Col. Our nanocomposite maintained an enhanced ability of biomineralization as compared to its pure counterparts. Molecular investigations revealed an elevated level of osteogenic markers as compared to Ge1-Glu-Col and BGnW. All in all, Gel-Glu-Col/BGnW seems to be a potential candidate for the regeneration of bone tissue.
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Affiliation(s)
- Esmat Azizipour
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hossein Aghamollaei
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Raheleh Halabian
- Applied Microbiology Research Center, Baqiyatallah University Medical of Sciences, Tehran, Iran
| | - Delaram Poormoghadam
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mostafa Saffari
- Department of Pharmaceutics, School of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Ali Salimi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Seo SJ, Kim YG. Improved bone regeneration using collagen-coated biphasic calcium phosphate with high porosity in a rabbit calvarial model. ACTA ACUST UNITED AC 2020; 16:015012. [PMID: 33325377 DOI: 10.1088/1748-605x/abb1fc] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Many growth factors have been paired with synthetic bone grafts to accelerate the healing process in vivo. Collagen has been particularly examined as a mediator of the enhancement of bone regeneration. This study investigated the new bone formation potential of micro-macroporous biphasic calcium phosphate (m-BCP), high porosity biphasic calcium phosphate (p-BCP), and collagen-coated p-BCP (cp-BCP) using a rabbit calvarial defect model. At 2 or 8 weeks after surgery, bone tissue was collected. The three-dimensional analysis of new bone formation using synchrotron radiation micro-computed tomography and histological study were conducted. The new bone formation values observed at 2 and 8 weeks in the negative control, m-BCP, p-BCP, and cp-BCP groups were 11.21 ± 1.36 mm3, 21.75 ± 1.18 mm3, 24.59 ± 1.26 mm3, and 29.54 ± 2.72 mm3, respectively, and 18.34 ± 3.99 mm3, 32.27 ± 3.78 mm3, 43.12 ± 1.61 mm3, and 58.20 ± 3.84 mm3, respectively. New bone formation was greatest in the cp-BCP group, while the amount of new bone at 8 weeks was higher than at 2 weeks in each group. The use of cp-BCP to enhance new bone formation during the healing period could improve bone regeneration.
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Affiliation(s)
- Seung-Jun Seo
- Department of Periodontology, School of Dentistry, A3DI, Kyungpook National University, Daegu 41940, Republic of Korea
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18
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Kanai R, Kuroshima S, Kamo M, Sasaki M, Uto Y, Inaba N, Uchida Y, Hayano H, Tamaki S, Inoue M, Sawase T. Effects of surface sub-micrometer topography following oxalic acid treatment on bone quantity and quality around dental implants in rabbit tibiae. Int J Implant Dent 2020; 6:75. [PMID: 33244653 PMCID: PMC7691415 DOI: 10.1186/s40729-020-00275-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 10/27/2020] [Indexed: 11/26/2022] Open
Abstract
Background To explore the effects of topographical modification of titanium substrates at submicron level by oxalic acid treatment on bone quality and quantity around dental implants in rabbit tibiae. Methods A total of 60 blasted CP-grade IV titanium dental implants were used. Twenty-eight control implant surfaces were treated with a mixture of HCl/H2SO4, whereas 28 other test implant surfaces were treated with oxalic acid following HCl/H2SO4 treatment. Two randomly selected sets of control or test implants were placed in randomly selected proximal tibiae of 14 female Japanese white rabbits. Euthanasia was performed 4 and 8 weeks post-implant placement. Bone to implant contact (BIC), bone area fraction (BAF), ratios of mature and immature bone to total bone, and the amount and types of collagen fibers were evaluated quantitatively. Two control and two test implants were used to analyze surface characteristics. Results Treatment by oxalic acid significantly decreased Sa and increased Ra of test implant surfaces. BIC in test implants was increased without alteration of BAF and collagen contents at 4 and 8 weeks after implant placement when compared with control implants. The ratios of immature and mature bone to total bone differed significantly between groups at 4 weeks post-implantation. Treatment by oxalic acid increased type I collagen and decreased type III collagen in bone matrices around test implants when compared with control implants at 8 weeks after implant placement. The effects of topographical changes of implant surfaces induced by oxalic acid on BAF, mature bone, collagen contents, and type I collagen were significantly promoted with decreased immature bone formation and type III collagen in the later 4 weeks post-implantation. Conclusions Treatment of implant surfaces with oxalic acid rapidly increases osseointegration from the early stages after implantation. Moreover, submicron topographical changes of dental implants induced by oxalic acid improve bone quality based on bone maturation and increased production of type I collagen surrounding dental implants in the late stage after implant placement. Supplementary Information The online version contains supplementary material available at 10.1186/s40729-020-00275-x.
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Affiliation(s)
- Riho Kanai
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Shinichiro Kuroshima
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan.
| | - Michimasa Kamo
- Research Section, Medical Division, KYOCERA Corporation, Yasu, 520-2362, Japan
| | - Muneteru Sasaki
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Yusuke Uto
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Nao Inaba
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Yusuke Uchida
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Hiroki Hayano
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Saki Tamaki
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Maaya Inoue
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
| | - Takashi Sawase
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan
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Padash A, Halabian R, Salimi A, Kazemi NM, Shahrousvand M. Osteogenic differentiation of mesenchymal stem cells on the bimodal polymer polyurethane/polyacrylonitrile containing cellulose phosphate nanowhisker. Hum Cell 2020; 34:310-324. [PMID: 33090371 DOI: 10.1007/s13577-020-00449-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/09/2020] [Indexed: 11/26/2022]
Abstract
Polycaprolactone diol is the cornerstone, equipped with polyacrylonitrile and cellulose nanowhiskers (CNWs), of biocompatible and biodegradable polyurethanes (PUs). The solvent casting/particulate leaching technique was employed to contracting foam scaffolds with bimodal sizes from the combination of polyurethane/polyacrylonitrile/cellulose nanowhisker nanocomposites. Sugar and sodium chloride are components used as porogens to develop the leaching method and fabricate the 3D scaffolds. Incorporation of different percentages of cellulose nanowhisker leads to the various efficient structures with biodegradability and biocompatibility properties. All nanocomposites scaffolds, as revealed by MTT assay using mesenchymal stem cell (MSC) lines, were non-cytotoxic. PU/PAN/CNW foam scaffolds were used for osteogenic differentiation of human mesenchymal stem cells (hMSCs). Based on the results, PU/PAN/CNW nanocomposites could not only support osteogenic differentiation but can also enhance the proliferation of hMSCs in three-dimensional synthetic extracellular matrix.
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Affiliation(s)
- Arash Padash
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Raheleh Halabian
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Ali Salimi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Negar Motakef Kazemi
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Mohsen Shahrousvand
- Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran, Iran
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Ayturk UM, Scollan JP, Goz Ayturk D, Suh ES, Vesprey A, Jacobsen CM, Divieti Pajevic P, Warman ML. Single-Cell RNA Sequencing of Calvarial and Long-Bone Endocortical Cells. J Bone Miner Res 2020; 35:1981-1991. [PMID: 32427356 PMCID: PMC8265023 DOI: 10.1002/jbmr.4052] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 05/04/2020] [Accepted: 05/13/2020] [Indexed: 12/25/2022]
Abstract
Single-cell RNA sequencing (scRNA-Seq) is emerging as a powerful technology to examine transcriptomes of individual cells. We determined whether scRNA-Seq could be used to detect the effect of environmental and pharmacologic perturbations on osteoblasts. We began with a commonly used in vitro system in which freshly isolated neonatal mouse calvarial cells are expanded and induced to produce a mineralized matrix. We used scRNA-Seq to compare the relative cell type abundances and the transcriptomes of freshly isolated cells to those that had been cultured for 12 days in vitro. We observed that the percentage of macrophage-like cells increased from 6% in freshly isolated calvarial cells to 34% in cultured cells. We also found that Bglap transcripts were abundant in freshly isolated osteoblasts but nearly undetectable in the cultured calvarial cells. Thus, scRNA-Seq revealed significant differences between heterogeneity of cells in vivo and in vitro. We next performed scRNA-Seq on freshly recovered long bone endocortical cells from mice that received either vehicle or sclerostin-neutralizing antibody for 1 week. We were unable to detect significant changes in bone anabolism-associated transcripts in immature and mature osteoblasts recovered from mice treated with sclerostin-neutralizing antibody; this might be a consequence of being underpowered to detect modest changes in gene expression, because only 7% of the sequenced endocortical cells were osteoblasts and a limited portion of their transcriptomes were sampled. We conclude that scRNA-Seq can detect changes in cell abundance, identity, and gene expression in skeletally derived cells. In order to detect modest changes in osteoblast gene expression at the single-cell level in the appendicular skeleton, larger numbers of osteoblasts from endocortical bone are required. © 2020 American Society for Bone and Mineral Research.
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Affiliation(s)
- Ugur M Ayturk
- Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA.,Department of Orthopaedic Surgery, Weill Cornell Medical College, New York, NY, USA.,Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA
| | - Joseph P Scollan
- Department of Orthopaedic Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Didem Goz Ayturk
- Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA
| | - Eun Sung Suh
- Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA
| | - Alexander Vesprey
- Musculoskeletal Integrity Program, Hospital for Special Surgery, New York, NY, USA
| | - Christina M Jacobsen
- Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA.,Divisions of Endocrinology and Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.,Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Paola Divieti Pajevic
- Department of Translational Dental Medicine, Boston University Goldman School of Dental Medicine, Boston, MA, USA
| | - Matthew L Warman
- Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA.,Department of Genetics, Harvard Medical School, Boston, MA, USA
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21
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Kilmer CE, Battistoni CM, Cox A, Breur GJ, Panitch A, Liu JC. Collagen Type I and II Blend Hydrogel with Autologous Mesenchymal Stem Cells as a Scaffold for Articular Cartilage Defect Repair. ACS Biomater Sci Eng 2020; 6:3464-3476. [PMID: 33463160 PMCID: PMC8287628 DOI: 10.1021/acsbiomaterials.9b01939] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Collagen type II is a promising material to repair cartilage defects since it is a major component of articular cartilage and plays a key role in chondrocyte function. This study investigated the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) embedded within a 3:1 collagen type I to II blend (Col I/II) hydrogel or an all collagen type I (Col I) hydrogel. Glycosaminoglycan (GAG) production in Col I/II hydrogels was statistically higher than that in Col I hydrogels or pellet culture, and these results suggested that adding collagen type II promoted GAG production. Col I/II hydrogels had statistically lower alkaline phosphatase (AP) activity than pellets cultured in a chondrogenic medium. The ability of MSCs encapsulated in Col I/II hydrogels to repair cartilage defects was investigated by creating two cartilage defects in the femurs of rabbits. After 13 weeks, histochemical staining suggested that Col I/II blend hydrogels provided favorable conditions for cartilage repair. Histological scoring revealed a statistically higher cartilage repair score for the Col I/II hydrogels compared to either the Col I hydrogels or empty defect controls. Results from this study suggest that there is clinical value in the cartilage repair capabilities of our Col I/II hydrogel with encapsulated MSCs.
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Affiliation(s)
- Claire E. Kilmer
- Davidson School of Chemical Engineering, Purdue University,
West Lafayette, IN, 47907, USA
| | - Carly M. Battistoni
- Davidson School of Chemical Engineering, Purdue University,
West Lafayette, IN, 47907, USA
| | - Abigail Cox
- Department of Comparative Pathobiology, Purdue University,
West Lafayette, IN, 47907, USA
| | - Gert J. Breur
- Department of Veterinary Clinical Sciences, Purdue
University, West Lafayette, IN, 47907, USA
| | - Alyssa Panitch
- Weldon School of Biomedical Engineering, Purdue University,
West Lafayette, IN, 47907, USA
- School of Biomedical Engineering, University of California
Davis, Davis, CA, 95616, USA
| | - Julie C. Liu
- Davidson School of Chemical Engineering, Purdue University,
West Lafayette, IN, 47907, USA
- Weldon School of Biomedical Engineering, Purdue University,
West Lafayette, IN, 47907, USA
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22
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Mahendra CK, Tan LTH, Lee WL, Yap WH, Pusparajah P, Low LE, Tang SY, Chan KG, Lee LH, Goh BH. Angelicin-A Furocoumarin Compound With Vast Biological Potential. Front Pharmacol 2020; 11:366. [PMID: 32372949 PMCID: PMC7176996 DOI: 10.3389/fphar.2020.00366] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 03/10/2020] [Indexed: 12/14/2022] Open
Abstract
Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-β/BMP, Wnt/β-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.
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Affiliation(s)
- Camille Keisha Mahendra
- Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Subang Jaya, Malaysia
| | - Loh Teng Hern Tan
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Subang Jaya, Malaysia
- Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China
| | - Wai Leng Lee
- School of Science, Monash University Malaysia, Subang Jaya, Malaysia
| | - Wei Hsum Yap
- School of Biosciences, Taylor's University, Subang Jaya, Malaysia
| | - Priyia Pusparajah
- Medical Health and Translational Research Group, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya, Malaysia
| | - Liang Ee Low
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China
| | - Siah Ying Tang
- Chemical Engineering Discipline, School of Engineering, Monash University Malaysia, Subang Jaya, Malaysia
- Advanced Engineering Platform, Monash University Malaysia, Subang Jaya, Malaysia
| | - Kok Gan Chan
- International Genome Centre, Jiangsu University, Zhenjiang, China
- Division of Genetics and Molecular Biology, Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia
| | - Learn Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Subang Jaya, Malaysia
| | - Bey Hing Goh
- Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
- Health and Well-Being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Subang Jaya, Malaysia
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23
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Simeoli R, Fierabracci A. Insights into the Role of MicroRNAs in the Onset and Development of Diabetic Neuropathy. Int J Mol Sci 2019; 20:4627. [PMID: 31540445 PMCID: PMC6770207 DOI: 10.3390/ijms20184627] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 08/30/2019] [Accepted: 09/11/2019] [Indexed: 12/18/2022] Open
Abstract
Diabetic neuropathy is a serious complication of chronic hyperglycemia in diabetes patients. This complication can involve both peripheral sensorimotor and autonomic nervous system. The precise nature of injury to the peripheral nerves mediated by chronic hyperglycemia is unknown; however, several mechanisms have been proposed including polyol pathway activation, enhanced glycation of proteins and lipids, increased oxidative stress, and cytokine release in the site of injury. MicroRNAs (miRNAs) are small non-coding RNAs that mediate RNA interference by post-transcriptionally modulating gene expression and protein synthesis. Therefore, they have been implicated in several developmental, physiological, and pathophysiological processes where they modulate the expression of different proteins. Recently, miRNAs gained an increasing attention also for their role as diagnostic test in many diseases due to their stability in serum and their easy detection. Furthermore, recent studies suggest that miRNAs may be involved in diabetic neuropathy although their role in the onset and the development of this complication is not fully understood. In this review, we discuss the most recent literature providing evidence for miRNAs role in diabetic neuropathy opening new pathways to improve both early diagnosis and treatment of this complication.
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Affiliation(s)
- Raffaele Simeoli
- Infectivology and Clinical Trials Area, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.
| | - Alessandra Fierabracci
- Infectivology and Clinical Trials Area, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.
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24
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Lee T. Mechanical and Mechanosensing Properties of Tumor Affected Bone Cells Were Inhibited via PI3K/Akt Pathway. J Bone Metab 2019; 26:179-191. [PMID: 31555615 PMCID: PMC6746668 DOI: 10.11005/jbm.2019.26.3.179] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 08/29/2019] [Accepted: 08/30/2019] [Indexed: 12/16/2022] Open
Abstract
Background Osteolytic metastasis is a common destructive form of metastasis, in which there is an increased bone resorption but impaired bone formation. It is hypothesized that the changed mechanical properties of tumor affected bone cells could inhibit its mechanosensing, thus contributing to differences in bone remodeling. Methods Here, atomic force microscopy indentation on primary bone cells exposed to 50% conditioned medium from Walker 256 (W) carcinoma cell line or its adaptive tumor (T) cells was carried out. Nitric oxide levels of bone cells were monitored in response to low-magnitude, high-frequency (LMHF) vibrations. Results A stronger sustained inhibitive effect on bone cell viability and differentiation by T cells as compared to that of its cell line was demonstrated. This could be attributed to the higher levels of transforming growth factor-β1 (TGF-β1) in the T-conditioned medium as compared to W-conditioned medium. Bone cell elastic moduli in W and T-groups were found to decrease significantly by 61.0% and 69.6%, respectively compared to control and corresponded to filamentous actin changes. Nitric oxide responses were significantly inhibited in T-conditioned group but not in W-conditioned group. Conclusions It implied that a change in cell mechanical properties is not sufficient as an indicator of change in mechanosensing ability. Moreover, inhibition of phosphoinositide 3-kinase/Akt downstream signaling pathway of TGF-β1 alleviated the inhibition effects on mechanosensing in T-conditioned cells, further suggesting that growth factors such as TGF-β could be good therapeutic targets for osteoblast treatment.
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Affiliation(s)
- Taeyong Lee
- Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, Korea
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25
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Kashiuchi S, Miyazawa R, Nagata H, Shirai M, Shimizu M, Sone H, Kamiyama S. Effects of administration of glucosamine and chicken cartilage hydrolysate on rheumatoid arthritis in SKG mice. Food Funct 2019; 10:5008-5017. [PMID: 31355395 DOI: 10.1039/c9fo00981g] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Supplementation with cartilage constituents, such as glucosamine, chondroitin sulfate and collagen peptide, are believed to reduce pain associated with joint disorders, such as rheumatoid arthritis (RA). Here, we administered daily, 10 mg glucosamine or 100 mg chicken cartilage hydrolysate (CH) to SKG/Jcl mice, a model for spontaneous RA, for 5 weeks and evaluated their effects on RA development. In SKG mice, the administration of glucosamine had no reducing effect on RA score but suppressed the expression of Mmp13 and Col3a1 genes in articular cartilage. In contrast, administration of CH suppressed the RA score and levels of plasma interleukin-6 and interleukin-17 to half, although the differences were not significant. Mice administered with glucosamine also showed decreased bone strength of femur and these adverse effects could be eliminated when glucosamine was used in conjunction with CH. These results suggest that CH and glucosamine exert effects on different aspects in SKG mice.
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Affiliation(s)
- Shoko Kashiuchi
- Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture, 471 Ebigase, Higashi-ku, Niigata 950-8680, Japan.
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26
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K S, Vijayaraghavan N, Krishnan V. Time–dependent variation in expression patterns of Lysyl Oxidase, Type I Collagen and tropoelastin mRNA in response to orthodontic force application. Arch Oral Biol 2019; 102:218-224. [DOI: 10.1016/j.archoralbio.2019.04.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 04/08/2019] [Accepted: 04/27/2019] [Indexed: 01/27/2023]
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27
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Hickey JW, Dong Y, Chung JW, Salathe SF, Pruitt HC, Li X, Chang C, Fraser AK, Bessell CA, Ewald AJ, Gerecht S, Mao HQ, Schneck JP. Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2019; 31:e1807359. [PMID: 30968468 PMCID: PMC8601018 DOI: 10.1002/adma.201807359] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 02/04/2019] [Indexed: 05/17/2023]
Abstract
T cell therapies require the removal and culture of T cells ex vivo to expand several thousand-fold. However, these cells often lose the phenotype and cytotoxic functionality for mediating effective therapeutic responses. The extracellular matrix (ECM) has been used to preserve and augment cell phenotype; however, it has not been applied to cellular immunotherapies. Here, a hyaluronic acid (HA)-based hydrogel is engineered to present the two stimulatory signals required for T-cell activation-termed an artificial T-cell stimulating matrix (aTM). It is found that biophysical properties of the aTM-stimulatory ligand density, stiffness, and ECM proteins-potentiate T cell signaling and skew phenotype of both murine and human T cells. Importantly, the combination of the ECM environment and mechanically sensitive TCR signaling from the aTM results in a rapid and robust expansion of rare, antigen-specific CD8+ T cells. Adoptive transfer of these tumor-specific cells significantly suppresses tumor growth and improves animal survival compared with T cells stimulated by traditional methods. Beyond immediate immunotherapeutic applications, demonstrating the environment influences the cellular therapeutic product delineates the importance of the ECM and provides a case study of how to engineer ECM-mimetic materials for therapeutic immune stimulation in the future.
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Affiliation(s)
- John W Hickey
- Department of Biomedical Engineering, School of Medicine, Baltimore, MD, 21218, USA
- Institute for Cell Engineering, School of Medicine, Baltimore, MD, 21205, USA
- Department of Pathology, School of Medicine, Baltimore, MD, 21287, USA
- Translational Tissue Engineering Center, Baltimore, MD, 21287, USA
- Institute for NanoBioTechnology, Baltimore, MD, 21218, USA
| | - Yi Dong
- Graduate Program in Immunology, School of Medicine, Baltimore, MD, 21205, USA
| | - Jae Wook Chung
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Baltimore, MD, 21218, USA
| | - Sebastian F Salathe
- Department of Biology, Krieger School of Arts and Sciences, Baltimore, MD, 21218, USA
| | - Hawley C Pruitt
- Institute for NanoBioTechnology, Baltimore, MD, 21218, USA
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Baltimore, MD, 21218, USA
| | - Xiaowei Li
- Translational Tissue Engineering Center, Baltimore, MD, 21287, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Baltimore, MD, 21218, USA
| | - Calvin Chang
- Department of Biomedical Engineering, School of Medicine, Baltimore, MD, 21218, USA
- Translational Tissue Engineering Center, Baltimore, MD, 21287, USA
| | - Andrew K Fraser
- Department of Biomedical Engineering, School of Medicine, Baltimore, MD, 21218, USA
- Department of Cell Biology and Center for Cell Dynamics, School of Medicine, Baltimore, MD, 21205, USA
| | - Catherine A Bessell
- Graduate Program in Immunology, School of Medicine, Baltimore, MD, 21205, USA
| | - Andrew J Ewald
- Department of Biomedical Engineering, School of Medicine, Baltimore, MD, 21218, USA
- Department of Cell Biology and Center for Cell Dynamics, School of Medicine, Baltimore, MD, 21205, USA
- Department of Oncology, School of Medicine, Baltimore, MD, 21205, USA
| | - Sharon Gerecht
- Department of Biomedical Engineering, School of Medicine, Baltimore, MD, 21218, USA
- Institute for NanoBioTechnology, Baltimore, MD, 21218, USA
- Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Baltimore, MD, 21218, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Baltimore, MD, 21218, USA
- Physical Sciences-Oncology Center, Baltimore, MD, 21218, USA
| | - Hai-Quan Mao
- Department of Biomedical Engineering, School of Medicine, Baltimore, MD, 21218, USA
- Translational Tissue Engineering Center, Baltimore, MD, 21287, USA
- Institute for NanoBioTechnology, Baltimore, MD, 21218, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Baltimore, MD, 21218, USA
| | - Jonathan P Schneck
- Institute for Cell Engineering, School of Medicine, Baltimore, MD, 21205, USA
- Department of Pathology, School of Medicine, Baltimore, MD, 21287, USA
- Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA
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28
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Kim S, Kim TM. Generation of mesenchymal stem-like cells for producing extracellular vesicles. World J Stem Cells 2019; 11:270-280. [PMID: 31171955 PMCID: PMC6545523 DOI: 10.4252/wjsc.v11.i5.270] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 04/02/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with therapeutic potential against autoimmune diseases, inflammation, ischemia, and metabolic disorders. Contrary to the previous conceptions, recent studies have revealed that the tissue repair and immunomodulatory functions of MSCs are largely attributed to their secretome, rather than their potential to differentiate into desired cell types. The composition of MSC secretome encompasses cytokines and growth factors, in addition to the cell-derived structures known as extracellular vesicles (EVs). EVs are membrane-enclosed nanoparticles that are capable of delivering biomolecules, and it is now believed that MSC-derived EVs are the major players that induce biological changes in the target tissues. Based on these EVs’ characteristics, the potential of EVs derived from MSC (MSC-EV) in terms of tissue regeneration and immune modulation has grown during the last decade. However, the use of MSCs for producing sufficient amount of EVs has not been satisfactory due to limitations in the cell growth and large variations among the donor cell types. In this regard, pluripotent stem cells (PSCs)-derived MSC-like cells, which can be robustly induced and expanded in vitro, have emerged as more accessible cell source that can overcome current limitations of using MSCs for EV production. In this review, we have highlighted the methods of generating MSC-like cells from PSCs and their therapeutic outcome in preclinical studies. Finally, we have also discussed future requirements for making this cell-free therapy clinically feasible.
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Affiliation(s)
- Soo Kim
- Brexogen Research Center, Brexogen Inc., Seoul, Songpa-gu 05718, South Korea
| | - Tae Min Kim
- Graduate School of International Agricultural Technology and Institute of Green-Bio Science and Technology, Seoul National University, Gangwon-do, Pyeongchang 25354, South Korea
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29
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Pan X, Li Y, Abdullah AO, Wang W, Qi M, Liu Y. Micro/nano-hierarchical structured TiO 2 coating on titanium by micro-arc oxidation enhances osteoblast adhesion and differentiation. ROYAL SOCIETY OPEN SCIENCE 2019; 6:182031. [PMID: 31183132 PMCID: PMC6502366 DOI: 10.1098/rsos.182031] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 03/12/2019] [Indexed: 05/08/2023]
Abstract
Nano-structured and micro/nano-hierarchical structured TiO2 coatings were produced on polished titanium by the micro-arc oxidation (MAO) technique. This study was conducted to screen a suitable structured TiO2 coating for osteoblast adhesion and differentiation in dental implants. The formulation was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and wettability testing. Adhesion, proliferation and osteogenic differentiation of MG63 cells were analysed by SEM, Cell Counting Kit-8 (CCK-8) and quantitative real-time PCR. The micro/nano-hierarchical structured TiO2 coating with both slots and pores showed the best morphology and wettability. XRD analysis revealed that rutile predominated along with a minor amount of anatase in both TiO2 coatings. Adhesion and extension of MG63 cells on the micro/nano-hierarchical structured TiO2 coating were the most favourable. MG63 cells showed higher growth rates on the micro/nano-hierarchical structured TiO2 coating at 1 and 3 days. Osteogenic-related gene expression was markedly increased in the micro/nano-hierarchical structured TiO2 coating group compared with the polished titanium group at 7, 14 and 21 days. These results revealed the micro/nano-hierarchical structured TiO2 coating as a promising surface modification and suitable biomaterial for use with dental implants.
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Affiliation(s)
- Xumeng Pan
- School of Stomatology, China Medical University, Shenyang 110013, People's Republic of China
| | - Yada Li
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China
| | - Adil O. Abdullah
- School of Stomatology, China Medical University, Shenyang 110013, People's Republic of China
| | - Weiqiang Wang
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China
| | - Min Qi
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China
| | - Yi Liu
- School of Stomatology, China Medical University, Shenyang 110013, People's Republic of China
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30
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Cell response to plasma electrolytic oxidation surface-modified low-modulus β-type titanium alloys. Colloids Surf B Biointerfaces 2019; 176:176-184. [DOI: 10.1016/j.colsurfb.2018.12.064] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 12/18/2018] [Accepted: 12/22/2018] [Indexed: 12/24/2022]
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31
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Al-Wahabi A, Ser-Od T, Inoue K, Nakajima K, Matsuzaka K, Inoue T. Topography enhances Runx2 expression in outgrowing cells from iPS cell-derived embryoid bodies. J Biomed Mater Res B Appl Biomater 2019; 107:2288-2296. [PMID: 30735289 DOI: 10.1002/jbm.b.34321] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Revised: 11/15/2018] [Accepted: 12/29/2018] [Indexed: 11/07/2022]
Abstract
The effect of differing polystyrene substrate topographies on the osteogenic potential of the outgrowing cells (OGCs) formed from mouse-induced pluripotent stem (iPS) cells (miPSCs)-derived embryoid bodies (EBs) was investigated. Polystyrene substrates were sandblasted with 25, 50, and 150 μm aluminum oxide particles to obtain topographies with average Sa values of 0.6, 1.1, and 1.8 μm, respectively. 3D-SEM was used to evaluate substrate's topographies. Examination was done by scanning electron microscopy (SEM), by immunocytofluorescence (ICF) analysis for vinculin, Runx2 and collagen type I, and by quantitative RT-PCR (qRT-PCR) analysis for Runx2 and collagen type I. SEM and ICF analyses revealed that surface roughness caused cells elongation (2, 6, 8, 10 times for the NT, 0.6 μm, 1.1 μm, and 1.8 μm, respectively). Vinculin staining demonstrated how the Sa value affected cellular attachment to the substrate. FA points were randomly distributed on flat surfaces, but rough surfaces resulted in more concentrated FA points on the podia of the cells (11.7, 25.2, 26.7, 16.6 vinculin spots per 20 μm2 for the NT, 0.6 μm, 1.1 μm, and 1.8 μm, respectively). qRT-PCR revealed that Runx2 expression was highest on day 16 on surfaces with Sa of 0.6 μm and 1.1 μm. Collagen type I expression increased from day 0 to day 16, no significance was found among the groups. In conclusion, surface topography affects cell shape and expression of early osteogenic potential in OGC, particularly surfaces with Sa values of 0.6 μm and 1.1 μm which showed the highest concentration of FA points on podia. These findings could be utilized in the development of inner surface topographies of scaffolds used with iPSCs. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2288-2296, 2019.
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Affiliation(s)
- Akram Al-Wahabi
- Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan.,Oral Health Science Center, Tokyo Dental College, Tokyo, Japan
| | - Tungalag Ser-Od
- Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan.,Oral Health Science Center, Tokyo Dental College, Tokyo, Japan
| | - Kenji Inoue
- Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan.,Oral Health Science Center, Tokyo Dental College, Tokyo, Japan
| | - Kei Nakajima
- Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan.,Oral Health Science Center, Tokyo Dental College, Tokyo, Japan
| | - Kenichi Matsuzaka
- Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan.,Oral Health Science Center, Tokyo Dental College, Tokyo, Japan
| | - Takashi Inoue
- Department of Clinical Pathophysiology, Tokyo Dental College, Tokyo, Japan.,Oral Health Science Center, Tokyo Dental College, Tokyo, Japan
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Min HY, Sung YK, Kim EJ, Jang WG. OVO homologue-like 1 promotes osteoblast differentiation through BMP2 expression. J Cell Physiol 2018; 234:11842-11849. [PMID: 30523637 DOI: 10.1002/jcp.27821] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 11/09/2018] [Indexed: 11/06/2022]
Abstract
OVO homologue-like 1 (OVOL1) encodes a C2H2 zinc finger protein and is an evolutionarily conserved gene in mammals. The OVOL1 expression is required for development. However, the function of OVOL1 in bone metabolism remains unreported. Here, we show for the first time the role of OVOL1 in osteoblast differentiation. To determine the role of OVOL1 in osteogenic differentiation, we analyzed OVOL1 expression in the preosteoblastic cell line. OVOL1 messenger RNA expression was induced during osteoblast differentiation. In addition, OVOL1 overexpression enhanced the expression of osteogenic genes including bone morphogenetic protein 2 (BMP2), the inhibitor of DNA binding 1 (Id1), distal-less homeobox 5 (Dlx5), runt-related transcription factor 2 (Runx2), osteocalcin (OC), and alkaline phosphatase (ALP). Moreover, mineralization of the extracellular matrix was increased by OVOL1 overexpression in MC3T3-E1 cells. Furthermore, knockdown of the OVOL1 experiment demonstrated that OVOL1 is required for osteoblast differentiation. Collectively, these results suggest that OVOL1 function as an important regulator of osteoblast differentiation by inducing BMP2 expression in MC3T3-E1 cells.
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Affiliation(s)
- Hyeon-Young Min
- Department of Biotechnology, College of Engineering, Daegu University, Daegu, Korea.,Research Institute of Antiaging, Daegu University, Daegu, Korea
| | - Young Kwan Sung
- Department of Immunology, Kyungpook National University School of Medicine, Daegu, Korea
| | - Eun-Jung Kim
- Research Institute of Antiaging, Daegu University, Daegu, Korea.,Department of Immunology, Kyungpook National University School of Medicine, Daegu, Korea
| | - Won-Gu Jang
- Department of Biotechnology, College of Engineering, Daegu University, Daegu, Korea.,Research Institute of Antiaging, Daegu University, Daegu, Korea
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Li JJ, Pang LN, Wu S, Zeng MD. Advances in the Effect of Heavy Metals in Aquatic Environment on the Health Risks for Bone. ACTA ACUST UNITED AC 2018. [DOI: 10.1088/1755-1315/186/3/012057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Brook N, Brook E, Dharmarajan A, Dass CR, Chan A. Breast cancer bone metastases: pathogenesis and therapeutic targets. Int J Biochem Cell Biol 2018; 96:63-78. [DOI: 10.1016/j.biocel.2018.01.003] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 12/31/2017] [Accepted: 01/04/2018] [Indexed: 01/03/2023]
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Dawood AE, Manton DJ, Parashos P, Wong RH, Singleton W, Holden JA, O'Brien-Simpson NM, Reynolds EC. Biocompatibility and Osteogenic/Calcification Potential of Casein Phosphopeptide-amorphous Calcium Phosphate Fluoride. J Endod 2017; 44:452-457. [PMID: 29275851 DOI: 10.1016/j.joen.2017.11.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/15/2017] [Accepted: 11/05/2017] [Indexed: 01/28/2023]
Abstract
INTRODUCTION Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and CPP-ACP with fluoride (CPP-ACFP) have been shown to provide bioavailable ions to promote mineralization. Hence, the aim of this study was to evaluate the materials' biocompatibility and osteogenic/calcification potential for endodontic applications. METHODS Human and mouse osteoblast-like and fibroblast-like cell lines were incubated with 0.05%-3.0% w/v CPP-ACP and CPP-ACFP, and toxicity, proliferation, alkaline phosphatase, interleukin (IL)-1α, and IL-6 production, collagen type I, osteocalcin, and osteopontin production, and mineralization/calcification were determined. RESULTS CPP-ACP and CPP-ACFP were non-toxic and had no significant effect on proliferation or production of the inflammatory cytokine IL-1α. Alkaline phosphatase activity of the osteoblast-like cells was significantly increased (P < .05) by CPP-ACP and CPP-ACFP, as was the production of the osteotropic cytokine IL-6, the formation of calcium mineral deposits, and the secretion of mineralization-related proteins (collagen type I and osteocalcin). CONCLUSIONS CPP-ACP and CPP-ACFP are biocompatible and have the potential to induce osteoblastic differentiation and mineralization. Potential applications include apexification, perforation repair, vital pulp therapy, and regenerative endodontic procedures.
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Affiliation(s)
- Alaa E Dawood
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - David J Manton
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - Peter Parashos
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - Rebecca H Wong
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - William Singleton
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - James A Holden
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - Neil M O'Brien-Simpson
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia
| | - Eric C Reynolds
- Melbourne Dental School, Oral Health CRC, Bio21 Institute, The University of Melbourne, Melbourne, Australia.
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Ma J, Guo W, Gao M, Huang B, Qi Q, Ling Z, Chen Y, Hu H, Zhou H, Yu F, Chen K, Richards G, Lin J, Zhou Z, Xiao D, Zou X. Biomimetic matrix fabricated by LMP-1 gene-transduced MC3T3-E1 cells for bone regeneration. Biofabrication 2017; 9:045010. [PMID: 28930090 DOI: 10.1088/1758-5090/aa8dd1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Bone healing is regulated by multiple microenvironmental signals provided by the extracellular matrix (ECM). This study aimed to mimic the native osteoinductive microenvironment by developing an ECM using gene-transduced cells. The LIM mineralization protein-1 (LMP-1) gene was transferred to murine pre-osteoblast cells (MC3T3-E1) using lentiviral vectors. Western blotting assay indicated that the MC3T3-E1 cells expressed an increased level of bone morphologic protein-2, -4 and -7 (BMP-2, -4 and -7) after LMP-1 gene transduction. The transduced cells were then seeded into calcined bovine bone scaffolds and cultured for 7, 14, and 21 days to construct ECMs on the scaffolds. The ECM-scaffold composites were then decellularized using the freeze-drying method. Scaffolds without ECM deposition were used as controls. The composites and controls were implanted into critical-sized bone defects created in the distal femurs of New Zealand rabbits. Twelve weeks after the surgery, both microcomputed tomography and histologic results indicated that the 7-day-cell-modified ECM-scaffold composites induced bone regeneration with significantly larger volume, trabecular thickness and connectivity than the controls. However, the 14- and 21-day-cell-modified ECM-scaffold composites triggered sustained inflammation response even at 12 weeks after the surgery and showed less bone ingrowth and integration than their 7-day-cell-modified counterparts. In conclusion, these results highlight the viable gene transfer techniques for manipulating cells in a constructed microenvironment of ECM for bone regeneration. However, the unresolved inflammation relating to the duration of ECM modification needs to be considered.
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Affiliation(s)
- Junxuan Ma
- Department of Orthopedic, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliate Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China
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Lin HY, Peng ZX. Nanofibers grafted on titanium alloy: the effects of fiber alignment and density on osteoblast mineralization. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2017; 28:140. [PMID: 28819756 DOI: 10.1007/s10856-017-5951-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 07/31/2017] [Indexed: 06/07/2023]
Abstract
The surface of medical implant alloy Ti-6Al-4V was chemically modified to allow it to covalently bond with collagen/PVA nanofibers. These nanofibers were successfully attached to the Ti-6Al-4V surface in three different morphologies: randomly oriented high-density fiber, COL(H); randomly oriented low-density fiber, COL(L); and aligned high-density fiber, COL(A). The effects of the morphology of these covalently-bound collagen nanofibers on the growth and differentiation of osteoblasts were studied for 21 days. The low-density nanofibers covered approximately 80% of the Ti64 surface, while the high-density nanofibers covered nearly 100%. These covalently attached fibrous coatings remained attached to the metal surface after 3 weeks of cell culture. In the first week the aligned fibers of COL(A) allowed the osteoblasts to stretch and elongate in the direction of the fibers. This directional elongation was not seen in the cells on the randomly-oriented samples. Cells proliferated and differentiated on all three surfaces over time. By the end of the test, the amount of type I collagen secreted by the cells on COL(H) was the highest, while the degree of mineralization was highest on COL(A) among the three samples (p < 0.05). Different nanofiber morphologies changed the cell morphology and the secretion of cellular products. The mechanisms remained to be investigated. The surface of medical implant alloy Ti-6Al-4V was chemically modified to allow it to covalently bond with collagen/PVA nanofibers. The SEM micrographs in the top row show the random and aligned morphology of the collagen-PVA nanofibers. The nanofibers on COL(A) were aligned in the general direction indicated by the arrow. The second row are images from EDX titanium element mapping. The location of the titanium elements are shown as bright dots. The low-density nanofibers, COL(L), covered approximately 80% of the Ti64 surface, while the high-density nanofibers, COL(H) and COL(A), covered nearly 100%. All three surfaces demonstrated good biocompatibility for the cultured osteoblasts. The fiber alignment seemed to have an effect on early cellular morphology (day 7), collagen secretion and calcium deposition, while the density of the fibers seemed to have no significant effect on cell behavior. SEM micrographs of osteoblasts after 7 and 14 days of cell culture are shown in the third and fourth rows. The surface of COL(L) has more cell-free spots indicated by (*) on day 7 as other two surfaces were covered by cells. The nanofibers could no longer be observed and were covered with mineralized granules (circles) after 14 days of cell culture. The cells appear stretched out on the mineralized granules.
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Affiliation(s)
- Hsin-Yi Lin
- Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei, Taiwan, 106.
- Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan, 106.
| | - Zhao-Xiang Peng
- Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan, 106
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Yao Y, Deng Q, Sun C, Song W, Liu H, Zhou Y. A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells. Mol Med Rep 2017; 16:1991-2001. [PMID: 28656244 PMCID: PMC5562021 DOI: 10.3892/mmr.2017.6846] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 04/25/2017] [Indexed: 12/20/2022] Open
Abstract
It has been hypothesized that intervertebral disc degeneration is initiated by degeneration of the cartilage endplate (CEP), which is characterized by cartilage ossification. CEP‑derived stem cells (CESCs), with the potential for chondro‑osteogenic differentiation, may be responsible for the balance between chondrification and ossification in the CEP. The CEP remains in an avascular and hypoxic microenvironment; the present study observed that hypoxia was able to markedly inhibit the osteogenic differentiation of CESCs. This tissue‑specific CESC differentiation in response to a hypoxic microenvironment was physiologically important for the prevention of ossification in the CEP. In order to study the hypoxia‑regulated mechanisms underlying osteogenic differentiation of CESCs, a Human Transcriptome Array 2.0 was used to detect differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) during the osteogenic differentiation of CESCs under hypoxia, compared with those induced under normoxia. High‑throughput analysis of DEGs and ASGs demonstrated that genes in the complement pathway were enriched, which may be a potential mechanism underlying hypoxia inhibition of CESCs osteogenesis. The results of the present study may provide a basis for future mechanistic studies regarding gene expression levels and alternative splicing events during the hypoxia‑regulated inhibition of osteogenesis, which may be helpful in identifying targets for CEP degeneration therapy.
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Affiliation(s)
- Yuan Yao
- Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
| | - Qiyue Deng
- Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, P.R. China
| | - Chao Sun
- Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
| | - Weiling Song
- Department of Ophthalmology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Huan Liu
- Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
| | - Yue Zhou
- Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
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Kuroshima S, Kaku M, Ishimoto T, Sasaki M, Nakano T, Sawase T. A paradigm shift for bone quality in dentistry: A literature review. J Prosthodont Res 2017. [PMID: 28633987 DOI: 10.1016/j.jpor.2017.05.006] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
PURPOSE The aim of this study was to present the current concept of bone quality based on the proposal by the National Institutes of Health (NIH) and some of the cellular and molecular factors that affect bone quality. STUDY SELECTION This is a literature review which focuses on collagen, biological apatite (BAp), and bone cells such as osteoblasts and osteocytes. RESULTS In dentistry, the term "bone quality" has long been considered to be synonymous with bone mineral density (BMD) based on radiographic and sensible evaluations. In 2000, the NIH proposed the concept of bone quality as "the sum of all characteristics of bone that influence the bone's resistance to fracture," which is completely independent of BMD. The NIH defines bone quality as comprising bone architecture, bone turnover, bone mineralization, and micro-damage accumulation. Moreover, our investigations have demonstrated that BAp, collagen, and bone cells such as osteoblasts and osteocytes play essential roles in controlling the current concept of bone quality in bone around hip and dental implants. CONCLUSION The current concept of bone quality is crucial for understanding bone mechanical functions. BAp, collagen and osteocytes are the main factors affecting bone quality. Moreover, mechanical loading dynamically adapts bone quality. Understanding the current concept of bone quality is required in dentistry.
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Affiliation(s)
- Shinichiro Kuroshima
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki-city, Nagasaki 852-8588, Japan.
| | - Masaru Kaku
- Division of Bio-prosthodontics, Graduate School of Medical and Dental Science, Niigata University, 2-5274, Gakkocho-dori, Chuo-ku, Niigata-City, Niigata 951-8514, Japan
| | - Takuya Ishimoto
- Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita-city, Osaka 565-0871, Japan
| | - Muneteru Sasaki
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki-city, Nagasaki 852-8588, Japan
| | - Takayoshi Nakano
- Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita-city, Osaka 565-0871, Japan
| | - Takashi Sawase
- Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki-city, Nagasaki 852-8588, Japan
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Daneault A, Prawitt J, Fabien Soulé V, Coxam V, Wittrant Y. Biological effect of hydrolyzed collagen on bone metabolism. Crit Rev Food Sci Nutr 2017; 57:1922-1937. [PMID: 25976422 DOI: 10.1080/10408398.2015.1038377] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Osteoporosis is a chronic and asymptomatic disease characterized by low bone mass and skeletal microarchitectural deterioration, increased risk of fracture, and associated comorbidities most prevalent in the elderly. Due to an increasingly aging population, osteoporosis has become a major health issue requiring innovative disease management. Proteins are important for bone by providing building blocks and by exerting specific regulatory function. This is why adequate protein intake plays a considerable role in both bone development and bone maintenance. More specifically, since an increase in the overall metabolism of collagen can lead to severe dysfunctions and a more fragile bone matrix and because orally administered collagen can be digested in the gut, cross the intestinal barrier, enter the circulation, and become available for metabolic processes in the target tissues, one may speculate that a collagen-enriched diet provides benefits for the skeleton. Collagen-derived products such as gelatin or hydrolyzed collagen (HC) are well acknowledged for their safety from a nutritional point of view; however, what is their impact on bone biology? In this manuscript, we critically review the evidence from literature for an effect of HC on bone tissues in order to determine whether HC may represent a relevant alternative in the design of future nutritional approaches to manage osteoporosis prevention.
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Affiliation(s)
- Audrey Daneault
- a INRA, UMR 1019, UNH, CRNH Auvergne , Clermont-Ferrand , France.,b Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine , Clermont-Ferrand , France
| | | | | | - Véronique Coxam
- a INRA, UMR 1019, UNH, CRNH Auvergne , Clermont-Ferrand , France.,b Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine , Clermont-Ferrand , France
| | - Yohann Wittrant
- a INRA, UMR 1019, UNH, CRNH Auvergne , Clermont-Ferrand , France.,b Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine , Clermont-Ferrand , France
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ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13. PLoS Genet 2017; 13:e1006481. [PMID: 28158191 PMCID: PMC5291374 DOI: 10.1371/journal.pgen.1006481] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Accepted: 11/15/2016] [Indexed: 12/16/2022] Open
Abstract
ATP6V1H is a component of a large protein complex with vacuolar ATPase (V-ATPase) activity. We identified two generations of individuals in which short stature and osteoporosis co-segregated with a mutation in ATP6V1H. Since V-ATPases are highly conserved between human and zebrafish, we generated loss-of-function mutants in atp6v1h in zebrafish through CRISPR/Cas9-mediated gene knockout. Homozygous mutant atp6v1h zebrafish exhibited a severe reduction in the number of mature calcified bone cells and a dramatic increase in the expression of mmp9 and mmp13. Heterozygous adults showed curved vertebra that lack calcified centrum structure and reduced bone mass and density. Treatment of mutant embryos with small molecule inhibitors of MMP9 and MMP13 significantly restored bone mass in the atp6v1h mutants. These studies have uncovered a new, ATP6V1H-mediated pathway that regulates bone formation, and defines a new mechanism of disease that leads to bone loss. We propose that MMP9/MMP13 could be therapeutic targets for patients with this rare genetic disease. Osteoporosis, a major health problem worldwide, is characterized by low bone mineral density (BMD) and a propensity to fracture. Genetic factors are clearly the major determinants of BMD, but their identification and contribution to osteoporosis risk have been difficult to assess in humans. Genome-wide association studies (GWAS) have identified numerous sequence variants that influence BMD. The loci identified to date, however, account for only a small fraction of the total variation in BMD. Through analysis of a pedigree with an undiagnosed disease in which affected members have markedly low bone mass, we identify a novel and critical bone formation pathway, mediated through the gene ATP6V1H. Zebrafish lacking apt6vh1 demonstrate loss of bone mass, and exhibit increased mmp9 and mmp13 levels; inhibition of mmp9 and mmp13 led to the rescue of bone density defects. Here we show that happloinsufficiency of ATP6V1H is associated with osteoporosis in both humans and zebrafish. This study exemplifies the value of studying rare diseases to understand prevalent ones.
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Song M, Huo H, Cao Z, Han Y, Gao L. Aluminum Trichloride Inhibits the Rat Osteoblasts Mineralization In Vitro. Biol Trace Elem Res 2017; 175:186-193. [PMID: 27260532 DOI: 10.1007/s12011-016-0761-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 05/24/2016] [Indexed: 12/01/2022]
Abstract
Aluminum (Al) is an accumulative toxic metal. Excessive Al accumulation inhibits osteoblasts mineralization and induces osteoporosis. However, the inhibition mechanism of Al on the mineralization is not fully understood. Thus, in this study, the rat osteoblasts were cultured and exposed to 0 mmol L-1 (control group, CG) and 0.52 mmol L-1 aluminum trichloride (AlCl3, treatment group, TG) for 7, 14, and 21 days, respectively. We found that mineralized matrix nodules, the activity of bone alkaline phosphatase, the concentration of extracellular calcium, the mRNA expression of type-I collagen, the mRNA and protein expressions of osteopontin, osteocalcin, and bone sialoprotein were all decreased, while the concentration of extracellular phosphorus was increased in TG compared with CG with time prolonged. Taken together, these results indicated that AlCl3 inhibited osteoblasts mineralization in vitro.
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Affiliation(s)
- Miao Song
- College of Veterinary Medicine, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin, 150030, China
| | - Hui Huo
- College of Veterinary Medicine, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin, 150030, China
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, China
| | - Zheng Cao
- College of Veterinary Medicine, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin, 150030, China
| | - Yanfei Han
- College of Veterinary Medicine, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin, 150030, China
| | - Li Gao
- College of Veterinary Medicine, Northeast Agricultural University, No. 59 Mucai Street, Xiangfang District, Harbin, 150030, China.
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Felgueiras HP, Decambron A, Manassero M, Tulasne L, Evans MDM, Viateau V, Migonney V. Bone tissue response induced by bioactive polymer functionalized Ti6Al4V surfaces: In vitro and in vivo study. J Colloid Interface Sci 2016; 491:44-54. [PMID: 28012912 DOI: 10.1016/j.jcis.2016.12.023] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 12/13/2016] [Accepted: 12/14/2016] [Indexed: 11/18/2022]
Abstract
Ti6Al4V is commonly used for orthopedic applications. This study was designed to test the potentially added benefit of Ti6Al4V functionalized with a bioactive polymer poly(sodium styrene sulfonate) both in vitro and in vivo. Cell-based assays with MC3T3-E1 osteoblast-like cells were used to measure the cell adhesion strength, cell spreading, focal contact formation, cell differentiation and the mineralization of extracellular matrix on grafted and ungrafted Ti6Al4V discs in combination with FBS and collagen type I. Bone morphogenetic protein-2 (BMP-2) was also included in the cell differentiation assay. Results showed that the grafted surface combined with collagen I gave superior levels in every parameter tested with cell-based assays and was almost equivalent to BMP-2 for cell differentiation. In vivo testing was conducted in rabbits (n=42) with cylinders of grafted and ungrafted Ti6Al4V implanted in defects made to the femoral and lateral condyles and animals that were maintained to 1, 3 and 12months. Hydroxyapatite coated Ti6Al4V cylinders were included as a clinical reference control. Osseointegration was assessed post-mortem using histomorphometric analysis conducted on resin sections of explanted undecalcified bone. Two histomorphometric parameters, that of bone-to-implant contact and the bone area, were analyzed by a trained observer blinded to sample identity. Results showed osseointegration on grafted Ti6Al4V was marginally better than both ungrafted and hydroxyapatite coated Ti6Al4V. Overall, the study found that the grafted Ti6Al4V significantly promoted all aspects of osteogenesis tested in vitro and, although in vivo outcomes were less compelling, histomorphometry showed osseointegration of grafted Ti6Al4V implants was equivalent or better than controls.
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Affiliation(s)
- Helena P Felgueiras
- Laboratory of Biomaterials and Polymers of Specialty, LBPS-CSPBAT CNRS UMR 7244, Université Paris 13, Sorbonne Paris Cité, 93430 Villetaneuse, France.
| | - Adeline Decambron
- Laboratoire de Bioingénierie et Bioimagerie Ostéo-articulaires (B2OA), UMR 7052, Université Paris Diderot, 75010 Paris, France; École Nationale Vétérinaire d'Alfort, Service de Chirurgie, Université Paris Est, 94700 Maisons-Alfort, France
| | - Mathieu Manassero
- Laboratoire de Bioingénierie et Bioimagerie Ostéo-articulaires (B2OA), UMR 7052, Université Paris Diderot, 75010 Paris, France; École Nationale Vétérinaire d'Alfort, Service de Chirurgie, Université Paris Est, 94700 Maisons-Alfort, France
| | - Louise Tulasne
- École Nationale Vétérinaire d'Alfort, Service de Chirurgie, Université Paris Est, 94700 Maisons-Alfort, France
| | - Margaret D M Evans
- CSIRO Biomedical Materials Program, 11 Julius Avenue, North Ride, Sydney, NSW 2113, Australia
| | - Véronique Viateau
- Laboratoire de Bioingénierie et Bioimagerie Ostéo-articulaires (B2OA), UMR 7052, Université Paris Diderot, 75010 Paris, France; École Nationale Vétérinaire d'Alfort, Service de Chirurgie, Université Paris Est, 94700 Maisons-Alfort, France
| | - Véronique Migonney
- Laboratory of Biomaterials and Polymers of Specialty, LBPS-CSPBAT CNRS UMR 7244, Université Paris 13, Sorbonne Paris Cité, 93430 Villetaneuse, France
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Zhao Z, Wang Z, Ge C, Krebsbach P, Franceschi R. Healing Cranial Defects with AdRunx2-transduced Marrow Stromal Cells. J Dent Res 2016; 86:1207-11. [DOI: 10.1177/154405910708601213] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Marrow stromal cells (MSCs) include stem cells capable of forming all mesenchymal tissues, including bone. However, before MSCs can be successfully used in regeneration procedures, methods must be developed to stimulate their differentiation selectively to osteoblasts. Runx2, a bone-specific transcription factor, is known to stimulate osteoblast differentiation. In the present study, we tested the hypothesis that Runx2 gene therapy can be used to heal a critical-sized defect in mouse calvaria. Runx2-engineered MSCs displayed enhanced osteogenic potential and osteoblast-specific gene expression in vitro and in vivo. Runx2-expressing cells also dramatically enhanced the healing of critical-sized calvarial defects and increased both bone volume fraction and bone mineral density. These studies provide a novel route for enhancing osteogenesis that may have future therapeutic applications for craniofacial bone regeneration.
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Affiliation(s)
- Z. Zhao
- Program in Oral Health Sciences,
- Department of Periodontics and Oral Medicine, and
- Department of Biological and Material Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; and
- Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Z. Wang
- Program in Oral Health Sciences,
- Department of Periodontics and Oral Medicine, and
- Department of Biological and Material Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; and
- Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - C. Ge
- Program in Oral Health Sciences,
- Department of Periodontics and Oral Medicine, and
- Department of Biological and Material Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; and
- Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - P. Krebsbach
- Program in Oral Health Sciences,
- Department of Periodontics and Oral Medicine, and
- Department of Biological and Material Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; and
- Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - R.T. Franceschi
- Program in Oral Health Sciences,
- Department of Periodontics and Oral Medicine, and
- Department of Biological and Material Sciences, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; and
- Department of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USA
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Effects of Apatite Cement Containing Atelocollagen on Attachment to and Proliferation and Differentiation of MC3T3-E1 Osteoblastic Cells. MATERIALS 2016; 9:ma9040283. [PMID: 28773408 PMCID: PMC5502976 DOI: 10.3390/ma9040283] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 04/03/2016] [Accepted: 04/07/2016] [Indexed: 11/17/2022]
Abstract
To improve the osteoconductivity of apatite cement (AC) for reconstruction of bone defects after oral maxillofacial surgery, we previously fabricated AC containing atelocollagen (AC(ate)). In the present study, we examined the initial attachment, proliferation and differentiation of mouse osteoblastic cells (MC3T3-E1 cells) on the surface of conventional AC (c-AC), AC(ate) and a plastic cell dish. The number of osteoblastic cells showing initial attachment to AC(ate) was greater than those attached to c-AC and similar to the number attached to the plastic cell wells. We also found that osteoblastic cells were well spread and increased their number on AC(ate) in comparison with c-AC and the wells without specimens, while the amount of procollagen type I carboxy-terminal peptide (PIPC) produced in osteoblastic cells after three days on AC(ate) was greater as compared to the others. There was no significant difference in regard to alkaline phosphatase (ALP) activity and osteocalcin production by osteoblastic cells among the three surface types after three and six days. However, after 12 days, ALP activity and the produced osteocalcin were greater with AC(ate). In conclusion, AC(ate) may be a useful material with high osteoconductivity for reconstruction of bone defects after oral maxillofacial surgery.
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46
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Schulz MC, Kallweit MB, Kallweit S, Koch R, Lauer G, Mai R, Hoffmann T. Autogenous bone and a bovine bone substitute for ridge preservation: preliminary clinical and histologic findings. Aust Dent J 2016; 61:62-70. [DOI: 10.1111/adj.12313] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2015] [Indexed: 11/28/2022]
Affiliation(s)
- MC Schulz
- Department of Oral and Maxillofacial Surgery; Faculty of Medicine ‘Carl Gustav Carus’; Technische Universität Dresden; Dresden Germany
| | | | | | - R Koch
- Institute for Medical Informatics and Biometry; Faculty of Medicine ‘Carl Gustav Carus’; Technische Universität Dresden; Dresden Germany
| | - G Lauer
- Department of Oral and Maxillofacial Surgery; Faculty of Medicine ‘Carl Gustav Carus’; Technische Universität Dresden; Dresden Germany
| | - R Mai
- Department of Oral and Maxillofacial Surgery; Faculty of Medicine ‘Carl Gustav Carus’; Technische Universität Dresden; Dresden Germany
| | - T Hoffmann
- Department of Periodontology; Faculty of Medicine ‘Carl Gustav Carus’; Technische Universität Dresden; Dresden Germany
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47
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Yang DJ, Jeon JH, Lee SY, An HW, Park KO, Park KB, Kim S. Effects of Collagen Grafting on Cell Behaviors in BCP Scaffold with Interconnected Pore Structure. Biomater Res 2016; 20:3. [PMID: 26779345 PMCID: PMC4714428 DOI: 10.1186/s40824-016-0049-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 01/04/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study was to investigate the effect of collagen grafted porous biphasic calcium phosphate (BCP) on cell attachment, proliferation, and differentiation. Porous BCP scaffolds with interconnected micropore structure were prepared with were prepared and then grafted with a collagen type I. The hydroxyapatite (HA) and β-tricalcium phosphate (TCP) ratio of the TCP scaffolds was about 60/40 and the collagen was crosslinked on the TCP scaffold surface (collagen-TCP). RESULTS The sintered BCP scaffolds showed fully interconnected micropore structures with submicron-sized grains. The collagen crosslinking in the scaffolds was conducted using the the N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide (NHS) crosslinking method. The cell proliferation of collagen-BCP scaffolds showed a similar result to that of the BCP scaffolds. However, osteoblastic differentiation and cell attachment increased in the collagen-BCP scaffolds. CONCLUSIONS Collagen-BCP scaffold improved the cell attachment ability in early phase and osteoblastic differentiation.
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Affiliation(s)
- Dong-Jun Yang
- Department of Institute of Science & Technology, Megagen Implant, Jain-myeon, Gyeongsan, Gyeongbuk 712-852 Korea
| | - Jae-Hui Jeon
- School of Materials Science & Engineering, Yeungnam University, Gyeongsan, Gyeongbuk 712-749 Korea
| | - Sun-Young Lee
- Department of Institute of Science & Technology, Megagen Implant, Jain-myeon, Gyeongsan, Gyeongbuk 712-852 Korea
| | - Hyun-Wook An
- Department of Institute of Science & Technology, Megagen Implant, Jain-myeon, Gyeongsan, Gyeongbuk 712-852 Korea
| | - Keun Oh Park
- Department of Institute of Science & Technology, Megagen Implant, Jain-myeon, Gyeongsan, Gyeongbuk 712-852 Korea
| | - Kwang-Bum Park
- Department of Institute of Science & Technology, Megagen Implant, Jain-myeon, Gyeongsan, Gyeongbuk 712-852 Korea
| | - Sukyoung Kim
- School of Materials Science & Engineering, Yeungnam University, Gyeongsan, Gyeongbuk 712-749 Korea
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48
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Sika Deer Antler Collagen Type I-Accelerated Osteogenesis in Bone Marrow Mesenchymal Stem Cells via the Smad Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:2109204. [PMID: 27066099 PMCID: PMC4809101 DOI: 10.1155/2016/2109204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Accepted: 12/06/2015] [Indexed: 11/17/2022]
Abstract
Deer antler preparations have been used to strengthen bones for centuries. It is particularly rich in collagen type I. This study aimed to unravel part of the purported bioremedial effect of Sika deer antler collagen type I (SDA-Col I) on bone marrow mesenchymal stem cells. The results suggest that SDA-Col I might be used to promote and regulate osteoblast proliferation and differentiation. SDA-Col I might potentially provide the basis for novel therapeutic strategies in the treatment of bone injury and/or in scaffolds for bone replacement strategies. Finally, isolation of SDA-Col I from deer antler represents a renewable, green, and uncomplicated way to obtain a biomedically valuable therapeutic.
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49
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Oliveira MC, Arntz OJ, Blaney Davidson EN, van Lent PLEM, Koenders MI, van der Kraan PM, van den Berg WB, Ferreira AVM, van de Loo FAJ. Milk extracellular vesicles accelerate osteoblastogenesis but impair bone matrix formation. J Nutr Biochem 2015; 30:74-84. [PMID: 27012623 DOI: 10.1016/j.jnutbio.2015.11.017] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2015] [Revised: 11/07/2015] [Accepted: 11/20/2015] [Indexed: 01/01/2023]
Abstract
The claimed beneficial effect of milk on bone is still a matter for debate. Recently extracellular vesicles (EVs) that contain proteins and RNA were discovered in milk, but their effect on bone formation has not yet been determined. We demonstrated previously that bovine milk-derived EVs (BMEVs) have immunoregulatory properties. Our aim was to evaluate the effect of BMEVs on osteogenesis by mice and human mesenchymal stem cells (hMSCs). Oral delivery of two concentrations of BMEVs to female DBA/1J mice during 7weeks did not alter the tibia trabecular bone area; however, the osteocytes number increased. In addition, the highest dose of BMEVs markedly increased the woven bone tissue, which is more brittle. The exposure of hMSCs to BMEVs during 21days resulted in less mineralization but higher cell proliferation. Interestingly BMEVs reduced the collagen production, but enhanced the expression of genes characteristic for immature osteoblasts. A kinetic study showed that BMEVs up-regulated many osteogenic genes within the first 4days. However, the production of type I collagen and expression of its genes (COL1A1 and COL1A2) were markedly reduced at days 21 and 28. At day 28, BMEVs again lead to higher proliferation, but mineralization was significantly increased. This was associated with increased expression of sclerostin, a marker for osteocytes, and reduced osteonectin, which is associated to bone matrix formation. Our study adds BMEVs to the list of milk components that can affect bone formation and may shed new light on the contradictory claims of milk on bone formation.
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Affiliation(s)
- Marina C Oliveira
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais, Brazil
| | - Onno J Arntz
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | | | - Peter L E M van Lent
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Marije I Koenders
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Peter M van der Kraan
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Wim B van den Berg
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Adaliene V M Ferreira
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais Belo Horizonte, Minas Gerais, Brazil
| | - Fons A J van de Loo
- Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
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50
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Endo K, Anada T, Yamada M, Seki M, Sasaki K, Suzuki O. Enhancement of osteoblastic differentiation in alginate gel beads with bioactive octacalcium phosphate particles. Biomed Mater 2015; 10:065019. [DOI: 10.1088/1748-6041/10/6/065019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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