scholarly journals Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

1995 ◽  
Vol 43 (4) ◽  
pp. 447-457 ◽  
Author(s):  
D M Salter ◽  
J L Godolphin ◽  
M S Gourlay
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Articular Chondrocytes ◽  
Knee Joints ◽  
Matrix Composition ◽  
Epiphyseal Growth Plate ◽  
Surface Receptors ◽  
Cartilage Differentiation ◽  
Health And Disease ◽  
And Function

During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

scholarly journals The ciliary protein IFT88 controls post-natal cartilage thickness and influences development of osteoarthritis

2020 ◽  
Author(s):  
CR Coveney ◽  
L Zhu ◽  
J Miotla-Zarebska ◽  
B Stott ◽  
I Parisi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cell Biology ◽  
Articular Chondrocytes ◽  
Skeletal Development ◽  
Cartilage Degradation ◽  
Cartilage Thickness ◽  
Tissue Growth ◽  
Calcified Cartilage ◽  
Health And Disease

AbstractMechanical forces are known to drive cellular signalling programmes in cartilage development, health, and disease. Proteins of the primary cilium, implicated in mechanoregulation, control cartilage formation during skeletal development, but their role in post-natal cartilage is unknown. Ift88fl/fl and AggrecanCreERT2 mice were crossed to create a cartilage specific inducible knockout mouse AggrecanCreERT2;Ift88fl/fl. Tibial articular cartilage thickness was assessed, through adolescence and adulthood, by histomorphometry and integrity by OARSI score. In situ cell biology was investigated by immunohistochemistry (IHC) and qPCR of micro-dissected cartilage. OA was induced by destabilisation of the medial meniscus (DMM). Some mice were provided with exercise wheels in their cage. Deletion of IFT88 resulted in a reduction in medial articular cartilage thickness (atrophy) during adolescence from 102.57μm, 95% CI [94.30, 119.80] in control (Ift88fl/fl) to 87.36μm 95% CI [81.35, 90.97] in AggrecanCreERT2;Ift88fl/fl by 8-weeks p<0.01, and adulthood (104.00μm, 95% CI [100.30, 110.50] in Ift88fl/fl to 89.42μm 95% CI [84.00, 93.49] in AggrecanCreERT2;Ift88fl/fl, 34-weeks, p<0.0001) through a reduction in calcified cartilage. Thinning in adulthood was associated with spontaneous cartilage degradation. Following DMM, AggrecanCreERT2;Ift88fl/fl mice had increased OA (OARSI scores at 12 weeks Ift88fl/fl = 22.08 +/− 9.30, and AggrecanCreERT2;Ift88fl/fl = 29.83 +/− 7.69). Atrophy was not associated with aggrecanase-mediated destruction or chondrocyte hypertrophy. Ift88 expression positively correlated with Tcf7l2 and connective tissue growth factor. Cartilage thickness was restored in AggrecanCreERT2;Ift88fl/fl by voluntary wheel exercise. Our results demonstrate that ciliary IFT88 regulates cartilage thickness and is chondroprotective, potentially through modulating mechanotransduction pathways in articular chondrocytes.

scholarly journals PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
P. Klinger ◽  
S. Lukassen ◽  
F. Ferrazzi ◽  
A. B. Ekici ◽  
T. Hotfiel ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Target Genes ◽  
Articular Chondrocytes ◽  
Pigment Epithelium ◽  
Cartilage Tissue ◽  
Rna Seq ◽  
Chondrocyte Phenotype ◽  
Growth Plate Cartilage ◽  
Qrt Pcr

Objective.To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively.Methods.We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR.Results.Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes.Conclusions.PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

scholarly journals SOX9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation

2021 ◽  
Vol 118 (8) ◽  
pp. e2019152118
Author(s):  
Abdul Haseeb ◽  
Ranjan Kc ◽  
Marco Angelozzi ◽  
Charles de Charleroy ◽  
Danielle Rux ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Articular Chondrocytes ◽  
Treatment Options ◽  
Cell Lineage ◽  
Bmp Signaling ◽  
Conditional Knockout ◽  
Growth Plate Chondrocytes

Cartilage is essential throughout vertebrate life. It starts developing in embryos when osteochondroprogenitor cells commit to chondrogenesis, activate a pancartilaginous program to form cartilaginous skeletal primordia, and also embrace a growth-plate program to drive skeletal growth or an articular program to build permanent joint cartilage. Various forms of cartilage malformation and degeneration diseases afflict humans, but underlying mechanisms are still incompletely understood and treatment options suboptimal. The transcription factor SOX9 is required for embryonic chondrogenesis, but its postnatal roles remain unclear, despite evidence that it is down-regulated in osteoarthritis and heterozygously inactivated in campomelic dysplasia, a severe skeletal dysplasia characterized postnatally by small stature and kyphoscoliosis. Using conditional knockout mice and high-throughput sequencing assays, we show here that SOX9 is required postnatally to prevent growth-plate closure and preosteoarthritic deterioration of articular cartilage. Its deficiency prompts growth-plate chondrocytes at all stages to swiftly reach a terminal/dedifferentiated stage marked by expression of chondrocyte-specific (Mgp) and progenitor-specific (Nt5e and Sox4) genes. Up-regulation of osteogenic genes (Runx2, Sp7, and Postn) and overt osteoblastogenesis quickly ensue. SOX9 deficiency does not perturb the articular program, except in load-bearing regions, where it also provokes chondrocyte-to-osteoblast conversion via a progenitor stage. Pathway analyses support roles for SOX9 in controlling TGFβ and BMP signaling activities during this cell lineage transition. Altogether, these findings deepen our current understanding of the cellular and molecular mechanisms that specifically ensure lifelong growth-plate and articular cartilage vigor by identifying osteogenic plasticity of growth-plate and articular chondrocytes and a SOX9-countered chondrocyte dedifferentiation/osteoblast redifferentiation process.

scholarly journals CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage

2020 ◽  
Vol 21 (20) ◽  
pp. 7556
Author(s):  
Miho Kuwahara ◽  
Koichi Kadoya ◽  
Sei Kondo ◽  
Shanqi Fu ◽  
Yoshiko Miyake ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Transgenic Mice ◽  
Articular Chondrocytes ◽  
Knee Joints ◽  
Ccn Family ◽  
Human Knee ◽  
Protein Levels ◽  
Enhanced Expression ◽  
P53 Mrna

Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.

Clinical Application of the Basic Science of Articular Cartilage Pathology and Treatment

2020 ◽  
Vol 33 (11) ◽  
pp. 1056-1068
Author(s):  
Anna J. Schreiner ◽  
Aaron M. Stoker ◽  
Chantelle C. Bozynski ◽  
Keiichi Kuroki ◽  
James P. Stannard ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Basic Science ◽  
Treatment Strategies ◽  
Cartilage Defects ◽  
Treatment Algorithms ◽  
Relative Paucity ◽  
Health And Disease ◽  
And Function ◽  
Surgical Treatments ◽  
Articular Cartilage Defects

AbstractThe joint is an organ with each tissue playing critical roles in health and disease. Intact articular cartilage is an exquisite tissue that withstands incredible biologic and biomechanical demands in allowing movement and function, which is why hyaline cartilage must be maintained within a very narrow range of biochemical composition and morphologic architecture to meet demands while maintaining health and integrity. Unfortunately, insult, injury, and/or aging can initiate a cascade of events that result in erosion, degradation, and loss of articular cartilage such that joint pain and dysfunction ensue. Importantly, articular cartilage pathology affects the health of the entire joint and therefore should not be considered or addressed in isolation. Treating articular cartilage lesions is challenging because left alone, the tissue is incapable of regeneration or highly functional and durable repair. Nonoperative treatments can alleviate symptoms associated with cartilage pathology but are not curative or lasting. Current surgical treatments range from stimulation of intrinsic repair to whole-surface and whole-joint restoration. Unfortunately, there is a relative paucity of prospective, randomized controlled, or well-designed cohort-based clinical trials with respect to cartilage repair and restoration surgeries, such that there is a gap in knowledge that must be addressed to determine optimal treatment strategies for this ubiquitous problem in orthopedic health care. This review article discusses the basic science rationale and principles that influence pathology, symptoms, treatment algorithms, and outcomes associated with articular cartilage defects in the knee.

scholarly journals Single-Cell RNA-Seq Reveals Transcriptomic Heterogeneity and Post-Traumatic Osteoarthritis-Associated Early Molecular Changes in Mouse Articular Chondrocytes

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1462
Author(s):  
Aimy Sebastian ◽  
Jillian L. McCool ◽  
Nicholas R. Hum ◽  
Deepa K. Murugesh ◽  
Stephen P. Wilson ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Single Cell ◽  
Articular Chondrocytes ◽  
Cartilage Degeneration ◽  
Cell Types ◽  
Knee Joints ◽  
Molecular Changes ◽  
Post Traumatic ◽  
Joint Trauma ◽  
Functional Profiles

Articular cartilage is a connective tissue lining the surfaces of synovial joints. When the cartilage severely wears down, it leads to osteoarthritis (OA), a debilitating disease that affects millions of people globally. The articular cartilage is composed of a dense extracellular matrix (ECM) with a sparse distribution of chondrocytes with varying morphology and potentially different functions. Elucidating the molecular and functional profiles of various chondrocyte subtypes and understanding the interplay between these chondrocyte subtypes and other cell types in the joint will greatly expand our understanding of joint biology and OA pathology. Although recent advances in high-throughput OMICS technologies have enabled molecular-level characterization of tissues and organs at an unprecedented resolution, thorough molecular profiling of articular chondrocytes has not yet been undertaken, which may be in part due to the technical difficulties in isolating chondrocytes from dense cartilage ECM. In this study, we profiled articular cartilage from healthy and injured mouse knee joints at a single-cell resolution and identified nine chondrocyte subtypes with distinct molecular profiles and injury-induced early molecular changes in these chondrocytes. We also compared mouse chondrocyte subpopulations to human chondrocytes and evaluated the extent of molecular similarity between mice and humans. This work expands our view of chondrocyte heterogeneity and rapid molecular changes in chondrocyte populations in response to joint trauma and highlights potential mechanisms that trigger cartilage degeneration.

scholarly journals Acid-Sensing Ion Channel-1a in Articular Chondrocytes and Synovial Fibroblasts: A Novel Therapeutic Target for Rheumatoid Arthritis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yayun Xu ◽  
Feihu Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Ion Channel ◽  
Articular Chondrocytes ◽  
Distribution Channel ◽  
Bone Destruction ◽  
Synovial Fibroblasts ◽  
Synovial Inflammation ◽  
And Function ◽  
Chronic Autoimmune Disease

Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H+-activated cation channel family. Emerging evidence has suggested that ASIC1a plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). Specifically, ASIC1a could promote inflammation, synovial hyperplasia, articular cartilage, and bone destruction; these lead to the progression of RA, a chronic autoimmune disease characterized by chronic synovial inflammation and extra-articular lesions. In this review, we provided a brief overview of the molecular properties of ASIC1a, including the basic biological characteristics, tissue and cell distribution, channel blocker, and factors influencing the expression and function, and focused on the potential therapeutic targets of ASIC1a in RA and possible mechanisms of blocking ASIC1a to improve RA symptoms, such as regulation of apoptosis, autophagy, pyroptosis, and necroptosis of articular cartilage, and synovial inflammation and invasion of fibroblast-like cells in synovial tissue.

scholarly journals Characterisation of growth plate dynamics in murine models of osteoarthritis

2020 ◽  
Author(s):  
Hasmik J. Samvelyan ◽  
Kamel Madi ◽  
Anna E. Törnqvist ◽  
Behzad Javaheri ◽  
Katherine A. Staines
Keyword(s):  
Articular Cartilage ◽  
Growth Plate ◽  
Volume Fraction ◽  
Left Knee ◽  
Bone Volume ◽  
Knee Joints ◽  
Murine Models ◽  
Male Mice ◽  
Bone Volume Fraction ◽  
Plate Dynamics

AbstractBackgroundThe purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics predict those at risk of osteoarthritis.Methods8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was examined by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to GP bridging.ResultsHigher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely dispersed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes. 3-dimensional quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints.ConclusionsThe results confirm associations between aberrant chondrocyte hypertrophy marker expression and osteoarthritis pathology in a surgical and loaded murine model of osteoarthritis. Spatial variations in growth plate bridging formation revealed accelerated cartilage-bone transitions which may contribute to anatomical variation in vulnerability to osteoarthritis development in these models.

scholarly journals Age-related alterations of articular cartilage in pituitary adenylate cyclase–activating polypeptide (PACAP) gene–deficient mice

GeroScience ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 775-793 ◽  
Author(s):  
Vince Szegeczki ◽  
Balázs Bauer ◽  
Adél Jüngling ◽  
Balázs Daniel Fülöp ◽  
Judit Vágó ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Adenylate Cyclase ◽  
Bone Cells ◽  
Knee Joints ◽  
Matrix Composition ◽  
Pac1 Receptor ◽  
Age Related ◽  
Pituitary Adenylate Cyclase ◽  
Tissue Aging ◽  
Deficient Mice

Abstract Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionarly conserved neuropeptide which is produced by various neuronal and non-neuronal cells, including cartilage and bone cells. PACAP has trophic functions in tissue development, and it also plays a role in cellular and tissue aging. PACAP takes part in the regulation of chondrogenesis, which prevents insufficient cartilage formation caused by oxidative and mechanical stress. PACAP knockout (KO) mice have been shown to display early aging signs affecting several organs. In the present work, we investigated articular cartilage of knee joints in young and aged wild-type (WT) and PACAP KO mice. A significant increase in the thickness of articular cartilage was detected in aged PACAP gene–deficient mice. Amongst PACAP receptors, dominantly PAC1 receptor was expressed in WT knee joints and a remarkable decrease was found in aged PACAP KO mice. Expression of PKA-regulated transcription factors, Sox5, Sox9 and CREB, decreased both in young and aged gene deficient mice, while Sox6, collagen type II and aggrecan expressions were elevated in young but were reduced in aged PACAP KO animals. Increased expression of hyaluronan (HA) synthases and HA-binding proteins was detected parallel with an elevated presence of HA in aged PACAP KO mice. Expression of bone related collagens (I and X) was augmented in young and aged animals. These results suggest that loss of PACAP signaling results in dysregulation of cartilage matrix composition and may transform articular cartilage in a way that it becomes more prone to degenerate.

Sign in / Sign up

Export Citation Format

Share Document