Degenerative meniscus lesions have been associated with both osteoarthritis etiology and its progression. We, therefore, sought to establish a human meniscus ex vivo model to study the meniscal response to cytokine treatment using a proteomics approach. Lateral menisci were obtained from five knee‐healthy donors. The meniscal body was cut into vertical slices and further divided into an inner (avascular) and outer region. Explants were either left untreated (controls) or stimulated with cytokines. Medium changes were conducted every 3 days up to Day 21 and liquid chromatography–mass spectrometry was performed at all the time points for the identification and quantification of proteins. Mixed‐effect linear regression models were used for statistical analysis to estimate the effect of treatments versus control on protein abundance. Treatment by IL1ß increased release of cytokines such as interleukins, chemokines, and matrix metalloproteinases but a limited catabolic effect in healthy human menisci explants. Further, we observed an increased release of matrix proteins (collagens, integrins, prolargin, tenascin) in response to oncostatin M (OSM) + tumor necrosis factor (TNF) and TNF+interleukin‐6 (IL6) + sIL6R treatments, and analysis of semitryptic peptides provided additional evidence of increased catabolic effects in response to these treatments. The induced activation of catabolic processes may play a role in osteoarthritis development.
Purpose: Ligaments are short bands of fibrous connective tissues responsible for transmitting load from bone to bone across joints and to guide normal joint motion. Cruciate ligaments of the knee joint, in particular the anterior cruciate ligament (ACL) are commonly damaged due to age-related wear and tear or sports related incident, leading to individual pain, muscle atrophy, immobility and development of knee osteoarthritis. Injuries to canine cranial cruciate ligament (CCL) are similar to ACL injuries in man being also predisposed to traumatic injury and non-contact ligament injury. To date, there are no current treatment targets for the prevention of cruciate ligament degradation and eventual rupture. MicroRNAs (miRs) control the expression of many genes simultaneously and have been suggested as potential therapeutic targets for various disorders of the musculoskeletal tissues due to their relatively easy delivery to tissues. To date, there is little known on the role of miRs and its expression in cruciate ligaments during injury, which could provide targets for alternative medical management in canine CCL injury. It is our hypothesis that miRs are altered in dogs with and without CCL rupture. Methods: Disease-free CCLs were harvested from cadaveric canine knee joints (n¼4) and ruptured CCLs were collected during routine surgery to manage CCL rupture. RNA was extracted and qPCR was performed for seven selected miRs following a literature review. TargetScan (Version 7.2) was used to identify gene targets for differentially expressed miRs. Statistical analysis was undertaken using a t-test (a¼0.05) in Graphpad Prism software (Version 7). Results: Significantly higher expression was found for miR-29a (p¼ 0.039), miR-26a (p¼0.05), miR-133 (p¼0.001) and miR-129a (p¼ 0.05) in ruptured CCLs in comparison to disease-free CCLs. Predicated putative target genes for the differently expressed miRs were important extracellular matrix (ECM) genes such as collagen type I alpha-1 chain (COL1A1), collagen type V alpha-1 chain (COL5A1), tenomodulin (TNMD) and fibrillin-1 (FBN1). In addition, miRs putative target genes associated with ligament matrix breakdown such as a disintegrin and metalloproteinase with thrombospondin motifs 5, 7 and 9 (ADAMTS5, ADAMTS7, ADAMTS9), were also identified. Conclusions: Ligament injury results in severe physical, social, economic consequences to the affected individual and may lead to development of degenerative joint disease such as OA. This study indicated that miR-29a, miR-26a, miR-133 and miR-129a may be important regulators of CCL ECM during injury and could be used as potential targets to prevent and treat CCL rupture.Purpose: There is likely an inflammatory phenotype of OA where proinflammatory cytokines contribute to the pathogenesis. Degenerative meniscus lesions have been associated with both OA etiology and its progression. Thus, we sought to establish a human meniscus in vitro model to explore the meniscal tissue's response to cytokine treatment where we used a discovery proteomics ...
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