COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis

Abstract

Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzymes, but also ECM proteins, like the cartilage oligomeric matrix protein (COMP) and thrombospondin-4 (TSP-4). To date, the functional roles of these newly synthesized proteins in articular cartilage are still elusive. Therefore, we analyzed the involvement of both proteins in OA specific processes in in vitro studies, using porcine chondrocytes, isolated from femoral condyles. The effect of COMP and TSP-4 on chondrocyte migration was investigated in transwell assays and their potential to modulate the chondrocyte phenotype, protein synthesis and matrix formation by immunofluorescence staining and immunoblot. Our results demonstrate that COMP could attract chondrocytes and may contribute to a repopulation of damaged cartilage areas, while TSP-4 did not affect this process. In contrast, both proteins similarly promoted the synthesis and matrix formation of collagen II, IX, XII and proteoglycans, but inhibited that of collagen I and X, resulting in a stabilized chondrocyte phenotype. These data suggest that COMP and TSP-4 activate mechanisms to protect and repair the ECM in articular cartilage.

99mTc-NTP 15-5 is a companion radiotracer for assessing joint functional response to sprifermin (rhFGF-18) in a murine osteoarthritis model

“…Such PK/CK scintigraphic ratio increase after surgery agrees with previously published results from our group in the meniscectomy and papain models of OA 16 , 25 . Hypertrophic changes in PG have been widely described in OA cartilage as a first line reparative reaction via an early increased synthesis of extracellular matrix (ECM) in damaged areas being followed at a later stage by degenerative destruction 26 – 31 .…”

Thrombospondin 2 Promotes IL-6 Production in Osteoarthritis Synovial Fibroblasts via the PI3K/AKT/NF-κB Pathway

“…29 COMP/TSP5 is also a well-established cartilage destruction marker in osteoarthritis. 58 Several reports have proposed that COMP/TSP5 is a promising diagnostic and prognostic marker, as well as disease severity. COMP/TSP5 has shown promise as a diagnostic and prognostic indicator and as a marker of the disease severity and the effect of treatment.…”

The Attenuating Effect of Low-Intensity Pulsed Ultrasound on Hypoxia-Induced Rat Chondrocyte Damage in TMJ Osteoarthritis Based on TMT Labeling Quantitative Proteomic Analysis

“…In vivo , some scholars have revealed that Thbs4 is present in the articular cartilage but not in the growth plates of mice, which suggests low levels or even an absence of Thbs4 during the peak of articular cartilage development ( Jeschke et al, 2015 ). In vitro , Maly concluded that Thbs4 maintains porcine chondrocyte phenotype stability by promoting collagen and proteoglycan production ( Maly et al, 2021 ). Collagen IX has been shown to stabilize fibrous and proteoglycan networks, and Brachvogel’s study identified Thbs4 as a possible binding partner for collagen IX ( Brachvogel et al, 2013 ).…”