• IL-1β
• L-type calcium channels
• TGF-β
• bone marrow mesenchymal stem cells
• chondrocytes
• chondrogenesis
• intracellular calcium levels
• voltage-operated calcium channels

• 101079489-TWINFLAG HORIZON-WIDERA-2021-ACCESS-03-01 program: 382 "Twinning for Promoting Excellence, Ability and Knowledge to develop novel approaches for tar-383 geting inflammatory and degenerative age-related joint diseases"
• 953138 - EMAPS-Cardio European Social Fund project according to Horizon2020 programe - ElectroMechanoActive 385 Polymer-based Scaffolds for Heart-on-Chip (EMAPS-Cardio)

• articular cartilage
• chondroprogenitor cells
• osteoarthritis
• regenerative medicine
• stem cells

• Hes1
• Notch1
• Occlusal loading
• Temporomandibular joint
• Temporomandibular joint disc

• Animals
• Receptor, Notch1/metabolism
• Rats, Wistar
• Female
• Signal Transduction/physiology
• Rats
• Temporomandibular Joint/growth & development
• Temporomandibular Joint/metabolism
• Transcription Factor HES-1/metabolism
• X-Ray Microtomography
• Mandibular Condyle/pathology
• Bone Remodeling/physiology
• Disease Models, Animal
• Cartilage, Articular/pathology
• Cartilage, Articular/metabolism

• 3D5204014431 Jilin Provincial Scientific and Technological Development Program

• shoulder
• cartilage
• histology
• glenohumeral joints
• humeral heads
• collagen
• staining
• synovitis
• synovial tissues
• collagen type ii
• cuff tear arthropathy
• immunohistochemically

• cartilage
• chondroprogenitor
• fibronectin
• stem cell
• tissue engineering

• Scar Free Foundation
• Action Medical Research
• VTCT Foundation

• CD146
• Mesenchymal stem cells
• Periosteum
• Progenitor
• Prospective isolation

• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/cytology
• Humans
• Cell Differentiation
• Biomarkers/metabolism
• Cells, Cultured
• Phenotype
• Thy-1 Antigens/metabolism
• 5'-Nucleotidase/metabolism
• Osteogenesis
• Periosteum/cytology
• Periosteum/metabolism
• Cartilage/metabolism
• Cartilage/cytology
• GPI-Linked Proteins

• University of Auckland

• MSCs
• arthritis
• interference
• microenvironmental
• regeneration
• stem cell

• Chondrogenic progenitor cells
• Granulocyte-colony stimulating factor
• Osteochondral defects
• chondrocyte

• Mesenchymal stem cells
• Periosteum
• Progenitor
• Prospective isolation
• Skeletal stem cells

• Humans
• Adult
• Mice
• Animals
• Cell Differentiation
• Antigens, CD34
• Stem Cells
• Biomarkers
• Cell Adhesion Molecules
• Periosteum

• Articular cartilage
• Cartilage tissue engineering
• Knee joint-resident mesenchymal stem cells
• Mesenchymal stem cells (MSCs)
• Osteoarthritis

• Aged
• Adult
• Middle Aged
• Humans
• Tissue Engineering/methods
• Cartilage, Articular/physiology
• Osteoarthritis/metabolism
• Mesenchymal Stem Cells
• Knee Joint
• Mesenchymal Stem Cell Transplantation/methods

• articular inflammatory microenvironment
• cartilage repair
• fate decision
• spatial and temporal regulation
• stem cells

• Humans
• Regeneration/physiology
• Tissue Engineering/methods
• Stem Cells
• Cartilage, Articular/injuries
• Cartilage, Articular/physiology
• Wound Healing
• Arthritis

• 2019YFA0110600 National Key R&D Program of China
• 82102552 National Natural Science Foundation of China
• National Natural Science Foundation of China

• arthritis
• canine animal models
• mesenchymal stem cells
• tissue regeneration

• apoptosis
• biomechanics
• chondrocytes
• differentiation
• occlusion
• remodeling

• Mice
• Animals
• Cartilage, Articular/metabolism
• Temporomandibular Joint/metabolism
• Chondrocytes/metabolism
• Cell Differentiation

• National Natural Science Foundation of China (NSFC)

• osteoarthritis
• preclinical research

• Humans
• Osteoarthritis, Knee/drug therapy
• Chondrocytes
• Cartilage, Articular
• Signal Transduction
• Angiopoietins/metabolism
• Angiopoietins/pharmacology
• Angiopoietins/therapeutic use
• Angiopoietin-Like Protein 3

• Novartis Pharmaceuticals Corporation

• canine
• knee joint distraction
• mechanical loading
• proteoglycans
• tgf-β signalling

A mount of growing evidence has proven that cartilage-derived progenitor cells (CPCs) harbor strong proliferation, migration, andmultiple differentiation potentials over the past 2 decades. CPCs in the stage of immature tissue play an important role in cartilage development process and injured cartilage repair in the young and active people. However, during maturation and aging, cartilage defects cannot be completely repaired by CPCs in vivo. Recently, tissue engineering has revealed that repaired cartilage defects with sufficient stem cell resources under good condition and bioactive scaffolds in vitro and in vivo. Chronic inflammation in the knee joint limit the proliferation and chondrogenesis abilities of CPCs, which further hampered cartilage healing and regeneration. Neocartilage formation was observed in the varus deformity of osteoarthritis (OA) patients treated with offloading technologies, which raises the possibility that organisms could rebuild cartilage structures spontaneously. In addition, nutritionmetabolismdysregulation, including glucose and free fatty acid dysregulation, could influence both chondrogenesis and cartilage formation. There are a few reviews about the advantages of CPCs for cartilage repair, but few focused on the reasons why CPCs could not repair the cartilage as they do in immature status. A wide spectrum of CPCs was generated by different techniques and exhibited substantial differences. We recently reported that CPCs maybe are as internal inflammation sources during cartilage inflammaging. In this review, we further streamlined the changes of CPCs from immature development to maturation and from healthy status to OA advancement. The key words including “cartilage derived stem cells”, “cartilage progenitor cells”, “chondroprogenitor cells”, “chondroprogenitors” were set for latest literature searching in PubMed and Web of Science. The articles were then screened through titles, abstracts, and the full texts in sequence. The internal environment including long-term inflammation, extendedmechanical loading, and nutritional elements intake and external deleterious factors were summarized. Taken together, these results provide a comprehensive understanding of the underlying mechanism of CPC proliferation and differentiation during development, maturation, aging, injury, and cartilage regeneration in vivo.

• National Natural Science Foundation of China
• China Postdoctoral Science Foundation

Osteoarthritis (OA) is the most prevalent chronic joint disease which increases in frequency with age eventually impacting most people over the age of 65. OA is the leading cause of disability and impaired mobility, yet the pathogenesis of OA remains unclear. Treatments have focused mainly on pain relief and reducing joint swelling. Currently there are no effective treatments to slow the progression of the disease and to prevent irreversible loss of cartilage. Here we demonstrate that stable expression of RORβ in cultured cells results in alteration of a gene program that is supportive of chondrogenesis and is protective against development of OA. Specifically, we determined that RORβ alters the ratio of expression of the FGF receptors FGFR1 (associated with cartilage destruction) and FGFR3 (associated with cartilage protection). Additionally, ERK1/2-MAPK signaling was suppressed and AKT signaling was enhanced. These results suggest a critical role for RORβ in chondrogenesis and suggest that identification of mechanisms that control the expression of RORβ in chondrocytes could lead to the development of disease modifying therapies for the treatment of OA.

During the development of the appendicular skeleton, the cartilaginous templates undergo hypertrophic differentiation and remodels into bone, except for the cartilage most adjacent to joint cavities where hypertrophic differentiation and endochondral bone formation are prevented, and chondrocytes instead form articular cartilage. The mechanisms that prevent hypertrophic differentiation and endochondral bone formation of the articular cartilage have not been elucidated. To explore the role of the synovial microenvironment in chondrocyte differentiation, osteochondral allografts consisting of articular cartilage, epiphyseal bone, and growth plate cartilage from distal femoral epiphyses of inbred Lewis rats expressing enhanced green fluorescent protein from a ubiquitous promoter were transplanted either in inverted or original (control) orientation to matching sites in wildtype littermates, thereby allowing for tracing of transplanted cells and their progenies. We found that no hypertrophic differentiation occurred in the growth plate cartilage ectopically placed at the joint surface. Instead, the transplanted growth plate cartilage, with time, remodeled into articular cartilage. This finding suggests that the microenvironment at the articular surface inhibits hypertrophic differentiation and supports articular cartilage formation. To explore this hypothesis, rat chondrocyte pellets were cultured with and without synoviocyte-conditioned media. Consistent with the hypothesis, hypertrophic differentiation was inhibited and expression of the articular surface marker lubricin (Prg4) was dramatically induced when chondrocyte pellets were exposed to synovium- or synoviocyte-conditioned media, but not to chondrocyte- or osteoblast-conditioned media. Taken together, we present evidence for a novel mechanism by which synoviocytes, through the secretion of a factor or factors, act directly on chondrocytes to inhibit hypertrophic differentiation and endochondral bone formation and promote articular cartilage formation. This mechanism may have important implications for articular cartilage development, maintenance, and regeneration.

Recent data suggest that cells isolated from osteoarthritic (OA) cartilage express mesenchymal progenitor cell (MPC) markers that have the capacity to form hyaline-like cartilage tissue. Whether or not these cells are influenced by the severity of OA remains unexplored. Therefore, we analyzed MPC marker expression and chondrogenetic potential of cells from mild, moderate and severe OA tissue. Human osteoarthritic tibial plateaus were obtained from 25 patients undergoing total knee replacement. Each sample was classified as mild, moderate or severe OA according to OARSI scoring. mRNA expression levels of MPC markers—CD105, CD166, Notch 1, Sox9; mature chondrocyte markers—Aggrecan (Acan), Col II A1, hypertrophic chondrocyte and osteoarthritis-related markers—Col I A1, MMP-13 and ALPL were measured at the tissue level (day 0), after 2 weeks of in vitro expansion (day 14) and following chondrogenic in vitro re-differentiation (day 35). Pellet matrix composition after in vitro chondrogenesis of different OA-derived cells was tested for proteoglycans, collagen II and I by safranin O and immunofluorescence staining. Multiple MPC markers were found in OA cartilage resident tissue within a single OA joint with no significant difference between grades except for Notch1, which was higher in severe OA tissues. Expression levels of CD105 and Notch 1 were comparable between OA cartilage-derived cells of different disease grades and bone marrow mesenchymal stem cell (BM-MSC) line (healthy control). However, the MPC marker Sox 9 was conserved after in vitro expansion and significantly higher in OA cartilage-derived cells compared to its levels in the BM-MSC. The in vitro expansion of cartilage-derived cells resulted in enrichment while re–differentiation in reduction of MPC markers for all three analyzed grades. However, only moderate OA-derived cells after the in vitro chondrogenesis resulted in the formation of hyaline cartilage-like tissue. The latter tissue samples were also highly positive for collagen II and proteoglycans with no expression of osteoarthritis-related markers (collagen I, ALPL and MMP13). MPC marker expression did not differ between OA grades at the tissue level. Interestingly after in vitro re-differentiation, only moderate OA-derived cells showed the capacity to form hyaline cartilage-like tissue. These findings may have implications for clinical practice to understand the intrinsic repair capacity of articular cartilage in OA tissues and raises the possibility of these progenitor cells as a candidate for articular cartilage repair.

• cartilage repair
• cartilage-resident stem/progenitor cells
• osteoarthritis
• proteoglycan 4
• superficial zone

• cartilage
• growth plate
• musculoskeletal health
• osteoarthritis
• regenerative medicine
• stem cells

• Articular cartilage
• Cellular senescence
• Chondrogenic progenitor cells
• Knee osteoarthritis
• Senescence-associated secretory phenotype

• Cartilage, Articular/metabolism
• Cartilage, Articular/pathology
• Chondrocytes
• Humans
• Interleukin-6/metabolism
• Interleukin-8/metabolism
• Osteoarthritis, Knee
• Senescence-Associated Secretory Phenotype
• Stem Cells/metabolism
• Stem Cells/pathology

• SACTAI
• SASP
• aging-related disease
• cell senescence
• mesenchymal stem cell

• Cell Communication
• Cellular Senescence/physiology
• Stem Cells
• Telomere

• P30 GM122732 NIGMS NIH HHS
• R33 AR076807 NIAMS NIH HHS
• R61 AR076807 NIAMS NIH HHS

Limited chondrocyte migration and impaired cartilage-to-cartilage healing is a barrier in cartilage regenerative therapy. Collagenase treatment and delivery of a chemotactic agent may play a positive role in chondrocyte repopulation at the site of cartilage damage. This study evaluated chondrocyte migratory activity after enzymatic treatment in cultured cartilage explant. Differential effects of platelet-derived growth factor (PDGF) dimeric isoforms on the migratory activity were investigated to define major chemotactic factors for cartilage.

Full-thickness cartilage (4-mm³ blocks) were harvested from porcine femoral condyles and subjected to explant culture. After 15 min or 60 min of actinase and collagenase treatments, chondrocyte migration and infiltration into a 0.5-mm cartilage gap was investigated. Cell morphology and lubricin, keratan sulfate, and chondroitin 4 sulfate expression in superficial- and deep-zone chondrocytes were assessed. The chemotactic activities of PDGF-AA, −AB, and -BB were measured in each zone of chondrocytes, using a modified Boyden chamber assay. The protein and mRNA expression and histological localization of PDGF-β were analyzed by western blot analysis, real-time reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry, and results in each cartilage zone were compared.

Superficial-zone chondrocytes had higher migratory activity than deep-zone chondrocytes and actively bridged the cartilage gap, while metachromatic staining by toluidine blue and immunoreactivities of keratan sulfate and chondroitin 4 sulfate were detected around the cells migrating from the superficial zone. These superficial-zone cells with weak immunoreactivity for lubricin tended to enter the cartilage gap and possessed higher migratory activity, while the deep-zone chondrocytes remained in the lacuna and exhibited less migratory activity. Among PDGF isoforms, PDGF-AB maximized the degree of chemotactic activity of superficial zone chondrocytes. Increased expression of PDGF receptor-β was associated with higher migratory activity of the superficial-zone chondrocytes.

In enzymatically treated cartilage explant culture, chondrocyte migration and infiltration into the cartilage gap was higher in the superficial zone than in the deep zone. Preferential expression of PDGF receptor-β combined with the PDGF-AB dimeric isoform may explain the increased migratory activity of the superficial-zone chondrocytes. Cells migrating from superficial zone may contribute to cartilage regeneration.

The online version contains supplementary material available at 10.1186/s12891-022-05210-2.

• Cartilage regeneration
• Lubricin
• Migratory activity
• Platelet-derived growth factor
• Superficial-zone chondrocyte

Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).

• cartilage
• clinical-tissue-cell level metrics
• cluster analysis
• osteoarthritis
• patient phenotypes

• Benchmarking
• Cytidine Triphosphate
• Humans
• Knee Joint/diagnostic imaging
• Knee Joint/pathology
• Osteoarthritis, Knee/diagnostic imaging
• Osteoarthritis, Knee/pathology
• Phenotype

• R01 AR063733 NIAMS NIH HHS

• chondrocytes
• osteoarthritis
• therapeutics

• cartilage regeneration
• groove model
• osteoarthritis

• ACI
• articular cartilage
• chondrocytes
• mesenchymal stem cells
• single-cell RNA sequencing

• articular cartilage
• cartilage repair
• endogenous
• osteoarthritis
• progenitor cell

Notch signaling has been identified as a critical regulator of cartilage development and homeostasis. Its pivotal role was established by both several joint specific Notch signaling loss of function mouse models and transient or sustained overexpression. NOTCH1 is the most abundantly expressed NOTCH receptors in normal cartilage and its expression increases in osteoarthritis (OA), when chondrocytes exit from their healthy “maturation arrested state” and resume their natural route of proliferation, hypertrophy, and terminal differentiation. The latter are hallmarks of OA that are easily evaluated in vitro in 2-D or 3-D culture models. The aim of our study was to investigate the effect of NOTCH1 knockdown on proliferation (cell count and Picogreen mediated DNA quantification), cell cycle (flow cytometry), hypertrophy (gene and protein expression of key markers such as RUNX2 and MMP-13), and terminal differentiation (viability measured in 3-D cultures by luminescence assay) of human OA chondrocytes. NOTCH1 silencing of OA chondrocytes yielded a healthier phenotype in both 2-D (reduced proliferation) and 3-D with evidence of decreased hypertrophy (reduced expression of RUNX2 and MMP-13) and terminal differentiation (increased viability). This demonstrates that NOTCH1 is a convenient therapeutic target to attenuate OA progression.

• angiogenesis
• chondrocytes
• hypertrophy
• osteoarthritis
• remodeling

• Aged
• Cell Culture Techniques, Three Dimensional
• Cells, Cultured
• Chondrocytes/metabolism
• Chondrocytes/pathology
• Core Binding Factor Alpha 1 Subunit/metabolism
• Female
• Humans
• Hypertrophy/etiology
• Hypertrophy/metabolism
• Hypertrophy/pathology
• Male
• Matrix Metalloproteinase 13/metabolism
• Osteoarthritis/etiology
• Osteoarthritis/metabolism
• Osteoarthritis/pathology
• Receptor, Notch1/metabolism
• Signal Transduction

• 3D-bioassembly
• cartilage tissues
• cocultured spheroids
• high throughput
• microtissues
• spheroid fusion
• tissue fusion

• Cells, Cultured
• Coculture Techniques
• Humans
• Models, Biological
• Spheroids, Cellular/metabolism
• Tissue Engineering/methods
• Tissue Scaffolds

• GL: XC University of Otago Health Sciences Fellowship
• 19/679 Zealand Health Research Council
• 21/802 Zealand Health Research Council
• 19/135 Zealand Health Research Council
• 15/483 Zealand Health Research Council
• 19/779 Zealand Health Research Council
• 18-UOO-016-CSG Royal Society Te Apārangi
• RDF-UOO1204 Royal Society Te Apārangi
• MFP-UOO1826 Royal Society Te Apārangi
• UOOX1407 Ministry for Business, Innovation & Employment
• Royal Society Te Apārangi

• Cellular senescence
• Chondrocyte
• Osteoarthritis
• Senescence associated secretory phenotype

Structural disturbances of the subchondral bone are a hallmark of osteoarthritis (OA), including sclerotic changes, cystic lesions, and osteophyte formation. Osteocytes act as mechanosensory units for the micro-cracks in response to mechanical loading. Once stimulated, osteocytes initiate the reparative process by recruiting bone-resorbing cells and bone-forming cells to maintain bone homeostasis. Osteocyte-expressed sclerostin is known as a negative regulator of bone formation through Wnt signaling and the RANKL pathway. In this review, we will summarize current understandings of osteocytes at the crossroad of allometry and mechanobiology to exploit the relationship between osteocyte morphology and function in the context of joint aging and osteoarthritis. We also aimed to summarize the osteocyte dysfunction and its link with structural and functional disturbances of the osteoarthritic subchondral bone at the molecular level. Compared with normal bones, the osteoarthritic subchondral bone is characterized by a higher bone volume fraction, a larger trabecular bone number in the load-bearing region, and an increase in thickness of pre-existing trabeculae. This may relate to the aberrant expressions of sclerostin, periostin, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, insulin-like growth factor 1, and transforming growth factor-beta, among others. The number of osteocyte lacunae embedded in OA bone is also significantly higher, yet the volume of individual lacuna is relatively smaller, which could suggest abnormal metabolism in association with allometry. The remarkably lower percentage of sclerostin-positive osteocytes, together with clustering of Runx-2 positive pre-osteoblasts, may suggest altered regulation of osteoblast differentiation and osteoblast-osteocyte transformation affected by both signaling molecules and the extracellular matrix. Aberrant osteocyte morphology and function, along with anomalies in molecular signaling mechanisms, might explain in part, if not all, the pre-osteoblast clustering and the uncoupled bone remodeling in OA subchondral bone.

• articular cartilage
• bone remodeling
• osteoarthritis
• osteocyte
• sclerostin

Recently, biomaterials for cartilage regeneration has been intensively investigated. However, the development of scaffolds that capture regenerated cartilage with biomechanical and structural recovery has rarely been reported. To address this challenge, platelet-rich plasma (PRP)-based cartilage constructs with a well-orchestrated symphony of cellular, biochemical and biomechanical elements were prepared by simultaneously employing chondrogenic progenitor cells (CPCs) as a cell source, optimizing platelet concentration, and adding an enzyme-ion activator. It was shown that this triple-optimized PRP + CPC construct possessed increased biomechanical properties and suitable biochemical signals. The following in vitro study demonstrated that the triple-optimized PRP + CPC constructs generated cartilage-like tissue with higher expression levels of chondrogenic-specific markers, more deposition of cartilage-specific extracellular matrix (ECM), and greater biomechanical values than those of the other constructs. Twelve weeks after the construct was implanted in a cartilage defect in vivo, histological analysis, qPCR, and biomechanical tests collectively showed that the triple-optimized constructs yielded a more chondrocyte-like cell phenotype with a higher synthesis of Col-II and aggrecan. More importantly, the triple-optimized constructs facilitated cartilage regeneration with better biomechanical recovery than that of the other constructs. These results demonstrate the efficacy of the triple-optimization strategy and highlight the simplicity and potency of this PRP + CPC construct for cartilage regeneration.

•

Cartilage tissue engineering has been intensively investigated.

• Biomechanical recovery
• Cartilage regeneration
• Platelet-rich plasma
• Structural recovery

• chondrocyte differentiation markers
• extracellular matrix
• hyaline cartilage development
• mouse
• nasal septum

• Articular cartilage
• EGFR
• Ki67
• Mechanical impact
• Metabolism
• Progenitor
• Sox9

• Age-associated diseases
• Cell senescence
• Mesenchymal stem cells
• Osteoarthritis
• Replication stress
• Senolytics

• P30 GM122732 NIGMS NIH HHS
• R33 AR076807 NIAMS NIH HHS
• R61 AR076807 NIAMS NIH HHS

• cartilage
• digital image analysis
• live-cell imaging
• osteoarthritis
• phase-contrast imaging
• stem and progenitor cells

• biomaterial scaffolds
• capacitive coupling
• computational modelling
• electrical stimulation
• electrically conductive hydrogels
• finite element analysis
• scaffold
• tissue engineering
• uncertainty quantification

• Cartilage/drug effects
• Cartilage/growth & development
• Electric Stimulation
• Humans
• Hydrogels/therapeutic use
• Models, Theoretical
• Regeneration/drug effects
• Tissue Engineering/methods
• Tissue Scaffolds/chemistry

• SFB 1270/1 - 299150580 Deutsche Forschungsgemeinschaft

• osteoimmunology
• mesenchymal stem cells

• Aggrecans/genetics
• Aggrecans/metabolism
• Cartilage, Articular/cytology
• Cartilage, Articular/physiology
• Cell Culture Techniques/methods
• Cells, Cultured
• Chondrogenesis/genetics
• Chondrogenesis/immunology
• Chondrogenesis/physiology
• Gene Expression/genetics
• Gene Expression Regulation, Developmental/genetics
• Humans
• Leptin/genetics
• Leptin/metabolism
• Osteoarthritis/genetics
• Osteoarthritis/physiopathology
• Osteopontin/genetics
• Osteopontin/metabolism
• Stem Cells/physiology
• Tissue Scaffolds

• MR/L02280X/1 Medical Research Council

• Cartilage regeneration
• Chemoattractants
• Endogenous cell recruitment
• Endogenous stem/progenitor cells
• Scaffold-based drug delivery systems

• HNK-1 trisaccharide
• aggrecan
• cellular regulation
• extracellular matrix
• glycosaminoglycan
• tissue morphogenesis

• Aggrecans/chemistry
• Aggrecans/physiology
• Aggrecans/therapeutic use
• Animals
• Biodiversity
• CD57 Antigens/physiology
• Cartilage/embryology
• Embryonic Development/physiology
• Glycosaminoglycans/chemistry
• Glycosaminoglycans/physiology
• Heart/embryology
• Heart/physiology
• Humans
• Neural Crest/physiology
• Neurogenesis/physiology
• Structure-Activity Relationship
• Weight-Bearing