scholarly journals Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5

2007 ◽  
Vol 56 (2) ◽  
pp. 575-585 ◽  
Author(s):  
Ruo-Hua Song ◽  
Micky D. Tortorella ◽  
Anne-Marie Malfait ◽  
James T. Alston ◽  
Zhiyong Yang ◽  
...  
2021 ◽  
Vol 22 (13) ◽  
pp. 6719
Author(s):  
Ashleigh M. Philp ◽  
Sam Butterworth ◽  
Edward T. Davis ◽  
Simon W. Jones

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1052 ◽  
Author(s):  
Simonetta Carluccio ◽  
Daniela Martinelli ◽  
Maria Elisabetta Federica Palamà ◽  
Rui Cruz Pereira ◽  
Roberto Benelli ◽  
...  

Regenerative strategies for human articular cartilage are still challenging despite the presence of resident progenitor cell population. Today, many efforts in the field of regenerative medicine focus on the use of platelet derivatives due to their ability to reactivate endogenous mechanisms supporting tissue repair. While their use in orthopedics continues, mechanisms of action and efficacy need further characterization. We describe that the platelet lysate (PL) is able to activate chondro-progenitor cells in a terminally differentiated cartilage tissue. Primary cultures of human articular chondrocytes (ACs) and cartilage explants were set up from donor hip joint biopsies and were treated in vitro with PL. PL recruited a chondro-progenitors (CPCs)-enriched population from ex vivo cartilage culture, that showed high proliferation rate, clonogenicity and nestin expression. CPCs were positive for in vitro tri-lineage differentiation and formed hyaline cartilage-like tissue in vivo without hypertrophic fate. Moreover, the secretory profile of CPCs was analyzed, together with their migratory capabilities. Some CPC-features were also induced in PL-treated ACs compared to fetal bovine serum (FBS)-control ACs. PL treatment of human articular cartilage activates a stem cell niche responsive to injury. These facts can improve the PL therapeutic efficacy in cartilage applications.


2000 ◽  
Vol 8 (5) ◽  
pp. 383-391 ◽  
Author(s):  
Wei Qiu ◽  
Martha Meaney Murray ◽  
Sonya Shortkroff ◽  
Cynthia R Lee ◽  
Scott D Martin ◽  
...  

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Evelyn Houtman ◽  
Margo Tuerlings ◽  
Janne Riechelman ◽  
Eka H. E. D. Suchiman ◽  
Robert J. P. van der Wal ◽  
...  

Abstract Background Failing of intrinsic chondrocyte repair after mechanical stress is known as one of the most important initiators of osteoarthritis. Nonetheless, insight into these early mechano-pathophysiological processes in age-related human articular cartilage is still lacking. Such insights are needed to advance clinical development. To highlight important molecular processes of osteoarthritis mechano-pathology, the transcriptome-wide changes following injurious mechanical stress on human aged osteochondral explants were characterized. Methods Following mechanical stress at a strain of 65% (65%MS) on human osteochondral explants (n65%MS = 14 versus ncontrol = 14), RNA sequencing was performed. Differential expression analysis between control and 65%MS was performed to determine mechanical stress-specific changes. Enrichment for pathways and protein-protein interactions was analyzed with Enrichr and STRING. Results We identified 156 genes significantly differentially expressed between control and 65%MS human osteochondral explants. Of note, IGFBP5 (FC = 6.01; FDR = 7.81 × 10−3) and MMP13 (FC = 5.19; FDR = 4.84 × 10−2) were the highest upregulated genes, while IGFBP6 (FC = 0.19; FDR = 3.07 × 10−4) was the most downregulated gene. Protein-protein interactions were significantly higher than expected by chance (P = 1.44 × 10−15 with connections between 116 out of 156 genes). Pathway analysis showed, among others, enrichment for cellular senescence, insulin-like growth factor (IGF) I and II binding, and focal adhesion. Conclusions Our results faithfully represent transcriptomic wide consequences of mechanical stress in human aged articular cartilage with MMP13, IGF binding proteins, and cellular senescence as the most notable results. Acquired knowledge on the as such identified initial, osteoarthritis-related, detrimental responses of chondrocytes may eventually contribute to the development of effective disease-modifying osteoarthritis treatments.


Cartilage ◽  
2021 ◽  
pp. 194760352110476
Author(s):  
Yannick Nossin ◽  
Eric Farrell ◽  
Wendy J.L.M. Koevoet ◽  
Frank Datema ◽  
Rodrigo A. Somoza ◽  
...  

Objective Cartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of complete cartilage releasate with functional assays in vitro and in vivo. Design We evaluated the gene expression profile of angiogenesis-related factors in healthy adult human articular cartilage with a transcriptome-wide analysis generated by next-generation RNAseq. The effect on angiogenesis of the releasate of cartilage tissue was assessed with a chick chorioallantoic membrane (CAM) assay as well as human umbilical vein endothelial cell (HUVEC) migration and proliferation assays using conditioned media generated from tissue-engineered cartilage derived from human articular and nasal septum chondrocytes as well as explants from bovine articular cartilage and human nasal septum. Experiments were done with triplicate samples of cartilage from 3 different donors. Results RNAseq data of 3 healthy human articular cartilage donors revealed that the majority of known angiogenesis-related factors expressed in healthy adult articular cartilage are pro-angiogenic. The releasate from generated cartilage as well as from tissue explants, demonstrated at least a 3.1-fold increase in HUVEC proliferation and migration indicating a pro-angiogenic effect of cartilage. Finally, the CAM assay demonstrated that cartilage explants can indeed attract vessels; however, their ingrowth was not observed. Conclusion Using multiple approaches, we show that cartilage releasate has an inherent pro-angiogenic capacity. It remains vessel free due to anti-invasive properties associated with the tissue itself.


Author(s):  
D. D. Chan ◽  
C. P. Neu

Articular cartilage and surrounding soft tissues in the knee are important to normal joint function. Osteoarthritis (OA) is highly prevalent in the United States [1] and features precocious degeneration of articular cartilage. Effective OA treatments require the ability to detect early degeneration, including mechanical and biochemical changes. Magnetic resonance imaging has shown promise for the detection of early degenerative changes, including various quantitative MRI techniques [2]. Displacement-encoded MRI has the ability to detect changes in mechanical behavior, and such techniques have previously been used in cartilage explants [3] and intact juvenile animal joints [4]. However, the authors are aware of no studies with displacement-encoded MRI of human articular cartilage. Tissue-level displacement patterns could be key to revealing early degeneration in articular cartilage. This study demonstrates for the first time displacement encoding with stimulated echoes (DENSE) in an adult human tibiofemoral joint.


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