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Deng J, Zeng X, Zhang K, Zhang T, Dong Y, Zou J, Wu C, Li Y, Li F, Guan Z. Knockdown of SMYD3 by RNA Interference Regulates the Expression of Autophagy-Related Proteins and Inhibits Bone Formation in Fluoride-Exposed Osteoblasts. Biol Trace Elem Res 2025; 203:2013-2028. [PMID: 39106008 PMCID: PMC11919934 DOI: 10.1007/s12011-024-04327-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/24/2024] [Indexed: 08/07/2024]
Abstract
This study aimed to explore the role of histone methyltransferase SET and MYND domain containing 3 (SMYD3) in bone metabolism of osteoblasts exposed to fluoride. The levels of urine fluoride, BALP, and OC and the mRNA expression of SMYD3 were determined in patients with skeletal fluorosis and non-fluoride-exposed people on informed consent. The expression of SMYD3 protein, OC contents, and BALP activities were detected in human osteoblast-like MG63 cells and rat primary osteoblasts treated with sodium fluoride (NaF) for 48 h. The autophagosomes were observed by transmission electron microscopy. Then, we knocked down SMYD3 to confirm whether it was involved in the regulation of bone formation and related to autophagy and Wnt/β-catenin pathway. We observed that OC and BALP levels in patients with skeletal fluorosis significantly increased, while the mRNA expression of SMYD3 significantly decreased in the skeletal fluorosis groups. In vitro, the OC contents, BALP activities, and expression of SMYD3 significantly increased, and many autophagosomes were observed in NaF treated osteoblasts. The downregulation of SMYD3 significantly inhibited OC contents, BALP activities, and expression of autophagy-related proteins, but with no significant changes in the Wnt/β-catenin pathway. Our results demonstrated that fluoride exposure with coal-burning pollution caused orthopedic injuries and abnormalities in the levels of OC and BALP and hindered normal bone metabolism. Silencing the SMYD3 gene could significantly reduce OC and BALP levels via inhibiting the increase in autophagy induced by fluoride.
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Affiliation(s)
- Jie Deng
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Xiaoxiao Zeng
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Kailin Zhang
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Department of Biochemistry and Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Ting Zhang
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Yangting Dong
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Jian Zou
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Changxue Wu
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Yi Li
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China
- Provincial Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, 550004, Guizhou, China
| | - Fucheng Li
- Research Group of Liupanshui Center for Disease Control and Prevention, Liupanshui, 553001, Guizhou, China
| | - Zhizhong Guan
- Key Laboratory of Endemic and Ethnic Diseases of the Ministry of Education, Guiyang, 550004, Guizhou, China.
- Departments of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou, China.
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Li T, Li W, Guo X, Tan T, Xiang C, Ouyang Z. Unraveling the potential mechanisms of the anti-osteoporotic effects of the Achyranthes bidentata-Dipsacus asper herb pair: a network pharmacology and experimental study. Front Pharmacol 2023; 14:1242194. [PMID: 37849727 PMCID: PMC10577322 DOI: 10.3389/fphar.2023.1242194] [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: 06/18/2023] [Accepted: 09/07/2023] [Indexed: 10/19/2023] Open
Abstract
Background: Osteoporosis is a prevalent bone metabolism disease characterized by a reduction in bone density, leading to several complications that significantly affect patients' quality of life. The Achyranthes bidentata-Dipsacus asper (AB-DA) herb pair is commonly used in Traditional Chinese Medicine (TCM) to treat osteoporosis. This study aimed to investigate the therapeutic compounds and potential mechanisms of AB-DA using network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. Methods: Identified compounds of AB-DA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), TCM@Taiwan Database, BATMAN-TCM, and relevant literature. The main bioactive ingredients were screened based on the criteria of "OB (oral bioavailability) ≥ 30, DL (drug-likeness) ≥ 0.18." Potential targets were predicted using the PharmMapper and SwissTargetPrediction websites, while disease (osteoporosis)-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The PPI network and KEGG/GO enrichment analysis were utilized for core targets and pathway screening in the STRING and Metascape databases, respectively. A drug-compound-target-pathway-disease network was constructed using Cytoscape software to display core regulatory mechanisms. Molecular docking and dynamics simulation techniques explored the binding reliability and stability between core compounds and targets. In vitro and in vivo validation experiments were utilized to explore the anti-osteoporosis efficiency and mechanism of sitogluside. Results: A total of 31 compounds with 83 potential targets for AB-DA against osteoporosis were obtained. The PPI analysis revealed several hub targets, including AKT1, CASP3, EGFR, IGF1, MAPK1, MAPK8, and MAPK14. GO/KEGG analysis indicated that the MAPK cascade (ERK/JNK/p38) is the main pathway involved in treating osteoporosis. The D-C-T-P-T network demonstrated therapeutic compounds that mainly consisted of iridoids, steroids, and flavonoids, such as sitogluside, loganic acid, and β-ecdysterone. Molecular docking and dynamics simulation analyses confirmed strong binding affinity and stability between core compounds and targets. Additionally, the validation experiments showed preliminary evidence of antiosteoporosis effects. Conclusion: This study identified iridoids, steroids, and flavonoids as the main therapeutic compounds of AB-DA in treating osteoporosis. The underlying mechanisms may involve targeting core MAPK cascade (ERK/JNK/p38) targets, such as MAPK1, MAPK8, and MAPK14. In vivo experiments preliminarily validated the anti-osteoporosis effect of sitogluside. Further in-depth experimental studies are required to validate the therapeutic value of AB-DA for treating osteoporosis in clinical practice.
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Affiliation(s)
- Tao Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wenzhao Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiaoning Guo
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Tingting Tan
- Department of Immunology, School of Basic Medical Science, Central South University, Changsha, Hunan, China
| | - Cheng Xiang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhengxiao Ouyang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Gu G, Hou D, Jiao G, Wu W, Zhou H, Wang H, Chen Y. Ortho-silicic Acid Plays a Protective Role in Glucocorticoid-Induced Osteoporosis via the Akt/Bad Signal Pathway In Vitro and In Vivo. Biol Trace Elem Res 2023; 201:843-855. [PMID: 35314965 DOI: 10.1007/s12011-022-03201-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 03/11/2022] [Indexed: 01/21/2023]
Abstract
Glucocorticoid-induced osteoporosis (GIOP) has been the most common form of secondary osteoporosis. Glucocorticoids (GCs) can induce osteocyte and osteoblast apoptosis. Plenty of research has verified that silicon intake would positively affect bone. However, the effects of silicon on GIOP are not investigated. In this study, we assessed the impact of ortho-silicic acid (OSA) on Dex-induced apoptosis of osteocytes by cell apoptosis assays. The apoptosis-related genes, cleaved-caspase-3, Bcl-2, and Bax, were detected by western blotting. Then, we evaluated the possible role of OSA on osteogenesis and osteoclastogenesis with Dex using Alizarin red staining and tartrate-resistant acid phosphatase (TRAP) staining. We also detected the related genes by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting. We then established the GIOP mouse model to evaluate the potential role of OSA in vivo. We found that OSA showed no cytotoxic on osteocytes below 50 μM and prevented MLO-Y4 from Dex-induced apoptosis. We also found that OSA promoted osteogenesis and inhibited osteoclastogenesis with Dex. OSA had a protective effect on GIOP mice via the Akt signal pathway in vivo. In the end, we verified the Akt/Bad signal pathway in vitro, which showed the same results. Our finding demonstrated that OSA could protect osteocytes from apoptosis induced by GCs both in vitro and in vivo. Also, it promoted osteogenesis and inhibited osteoclastogenesis with the exitance of Dex. In conclusion, OSA has the potential value as a therapeutic agent for GIOP.
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Affiliation(s)
- Guanghui Gu
- Qilu Hospital of Shandong University, Jinan, Shandong, China
- Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Dehui Hou
- Qilu Hospital of Shandong University, Jinan, Shandong, China
- Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Guangjun Jiao
- Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Wenliang Wu
- Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Hongming Zhou
- Department of Spine Surgery, Linyi Central Hospital, Linyi, Shandong, China
| | - Hongliang Wang
- Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yunzhen Chen
- Department of Spine Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
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4
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Duan Y, Su YT, Ren J, Zhou Q, Tang M, Li J, Li SX. Kidney tonifying traditional Chinese medicine: Potential implications for the prevention and treatment of osteoporosis. Front Pharmacol 2023; 13:1063899. [PMID: 36699069 PMCID: PMC9868177 DOI: 10.3389/fphar.2022.1063899] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 12/21/2022] [Indexed: 01/11/2023] Open
Abstract
The aging global population is increasingly affected by osteoporosis (OP), which is one of the most significant threats to the elderly. Moreover, its prevention and treatment situations have become increasingly severe. Therefore, it is imperative to develop alternatives or complementary drugs for preventing and treating osteoporosis. Kidney tonifying traditional Chinese medicine (KTTCM) has been used for the treatment of osteoporosis for a long time. Pharmacological studies have shown that kidney tonifying traditional Chinese medicine can promote osteoblasts, inhibit osteoclasts, and regulate the level of estrogen and plays vital roles in stimulating osteogenesis, restraining adipogenesis of marrow mesenchymal stem cells (MSCs), regulating the metabolism of calcium and phosphorus, and inhibiting oxidative stress. These effects are mediated by OPG/RANKL/RANK, BMP/Smads, MAPKs, and Wnt/β-catenin systems. To develop a safe, synergistic, effective, and homogenized TCM formula with robust scientific evidence to provide faster and more economical alternatives, the anti-osteoporosis ingredients and pharmacological mechanisms of kidney tonifying traditional Chinese medicine are recapitulated from the perspective of molecular and cell biology, and the safety and toxicity of kidney tonifying traditional Chinese medicine have also been reviewed in this paper.
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Affiliation(s)
- Yan Duan
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China,Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
| | - Yu-Ting Su
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China,Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
| | - Jie Ren
- Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
| | - Qun Zhou
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China,Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
| | - Min Tang
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China,Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
| | - Juan Li
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China,Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China
| | - Shun-Xiang Li
- Hunan Engineering Technology Research Center for Bioactive Substance Discovery of Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China,Hunan Province Sino-US International Joint Research Center for Therapeutic Drugs of Senile Degenerative Diseases, Changsha, China,*Correspondence: Shun-Xiang Li,
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5
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Yan CP, Wang XK, Jiang K, Yin C, Xiang C, Wang Y, Pu C, Chen L, Li YL. β-Ecdysterone Enhanced Bone Regeneration Through the BMP-2/SMAD/RUNX2/Osterix Signaling Pathway. Front Cell Dev Biol 2022; 10:883228. [PMID: 35669516 PMCID: PMC9164109 DOI: 10.3389/fcell.2022.883228] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 05/03/2022] [Indexed: 11/19/2022] Open
Abstract
Bone defects are a global public health problem. However, the available methods for inducing bone regeneration are limited. The application of traditional Chinese herbs for bone regeneration has gained popularity in recent years. β-ecdysterone is a plant sterol similar to estrogen, that promotes protein synthesis in cells; however, its function in bone regeneration remains unclear. In this study, we investigated the function of β-ecdysterone on osteoblast differentiation and bone regeneration in vitro and in vivo. MC3T3-E1 cells were used to test the function of β-ecdysterone on osteoblast differentiation and bone regeneration in vitro. The results of the Cell Counting Kit-8 assay suggested that the proliferation of MC3T3-E1 cells was promoted by β-ecdysterone. Furthermore, β-ecdysterone influenced the expression of osteogenesis-related genes, and the bone regeneration capacity of MC3T3-E1 cells was detected by polymerase chain reaction, the alkaline phosphatase (ALP) test, and the alizarin red test. β-ecdysterone could upregulate the expression of osteoblastic-related genes, and promoted ALP activity and the formation of calcium nodules. We also determined that β-ecdysterone increased the mRNA and protein levels of components of the BMP-2/Smad/Runx2/Osterix pathway. DNA sequencing further confirmed these target effects. β-ecdysterone promoted bone formation by enhancing gene expression of the BMP-2/Smad/Runx2/Osterix signaling pathway and by enrichment biological processes. For in vivo experiments, a femoral condyle defect model was constructed by drilling a bone defect measuring 3 mm in diameter and 4 mm in depth in the femoral condyle of 8-week-old Sprague Dawley male rats. This model was used to further assess the bone regenerative functions of β-ecdysterone. The results of micro-computed tomography showed that β-ecdysterone could accelerate bone regeneration, exhibiting higher bone volume, bone surface, and bone mineral density at each observation time point. Immunohistochemistry confirmed that the β-ecdysterone also increased the expression of collagen, osteocalcin, and bone morphogenetic protein-2 in the experiment group at 4 and 8 weeks. In conclusion, β-ecdysterone is a new bone regeneration regulator that can stimulate MC3T3-E1 cell proliferation and induce bone regeneration through the BMP-2/Smad/Runx2/Osterix pathway. This newly discovered function of β-ecdysterone has revealed a new direction of osteogenic differentiation and has provided novel therapeutic strategies for treating bone defects.
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Affiliation(s)
- Cai-Ping Yan
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xing-Kuan Wang
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ke Jiang
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Chong Yin
- Laboratory for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space Biosciences and Biotechnology, NPU-UAB Joint Laboratory for Bone Metabolism, Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an, China
| | - Chao Xiang
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yong Wang
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Chaoyu Pu
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Lu Chen
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yu-Ling Li
- Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.,Laboratory of Biological Tissue Engineering and Digital Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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Shuvalov O, Fedorova O, Tananykina E, Gnennaya Y, Daks A, Petukhov A, Barlev NA. An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms. Front Pharmacol 2020; 11:561537. [PMID: 33192507 PMCID: PMC7663021 DOI: 10.3389/fphar.2020.561537] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 09/30/2020] [Indexed: 12/30/2022] Open
Abstract
Ecdysterone (Ecdy) is a hormone found in arthropods, which regulates their development. It is also synthesized by a number of plants to combat insect pests. It provides a number of beneficial pharmacological effects including the anabolic and adaptogenic ones. Ecdysterone is widely marketed as food supplement to enhance the physical performance of athletes. In addition to the estrogen receptor beta (ERbeta)-dependent anabolic effect of Ecdy in muscles, the molecular mechanisms of the plethora of other Ecdy-induced pharmacological effects remain unknown. The aim of this study was to investigate the pharmacological effect of ecdysterone on human breast cancer cell lines of different molecular subtypes. Surprisingly, in contrast to the anabolic effect on muscle tissues, we have revealed a tumor suppressive effect of Ecdy on a panel of breast cancer cell lines studied. Using the SeaHorse-based energy profiling, we have demonstrated that Ecdy dampened glycolysis and respiration, as well as greatly reduced the metabolic potential of triple negative breast cancer cell lines. Furthermore, we have revealed that Ecdy strongly induced autophagy. As part of the combined treatment, based on the Combination Index (CI) and Dose Reduction Index (DRI), Ecdy synergized with doxorubicin to induce cell death in several breast cancer cell lines. In contrast, Ecdy had only minor effect on non-transformed human fibroblasts. Collectively, our results indicate that ecdysterone can be considered as a new potential adjuvant for genotoxic therapy in treatment of breast cancer patients.
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Affiliation(s)
- O Shuvalov
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia
| | - O Fedorova
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia
| | - E Tananykina
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia
| | - Y Gnennaya
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia
| | - A Daks
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia
| | - A Petukhov
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia.,Almazov National Medical Research Centre, St-Petersburg, Russia
| | - N A Barlev
- Institute of cytology, Russian Academy of Sciences (RAS), St-Petersburg, Russia.,Moscow Institute of Physics and Technology, Dolgoprudny, Russia.,Orekhovich Institute of Biochemical Medicine, Moscow, Russia
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7
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Biological Factors, Metals, and Biomaterials Regulating Osteogenesis through Autophagy. Int J Mol Sci 2020; 21:ijms21082789. [PMID: 32316424 PMCID: PMC7215394 DOI: 10.3390/ijms21082789] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/10/2020] [Accepted: 04/13/2020] [Indexed: 01/18/2023] Open
Abstract
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. This review provides a revision of the literature on all the exogen factors that can modulate osteogenesis through autophagy regulation. Metal ion exposition, mechanical stimuli, and biological factors, including hormones, nutrients, and metabolic conditions, were taken into consideration for their ability to tune osteogenic differentiation through autophagy. In addition, an exhaustive overview of biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is provided as well. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for finely tailoring innovative therapeutic treatments and designing novel biomaterials.
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