Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells.

Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis.

Osteopontin level in synovial fluid is associated with the severity of joint pain and cartilage degradation after anterior cruciate ligament rupture.

OBJECTIVE: To explore the molecular function of Osteopontin (OPN) in the pathogenesis of human OA, we compared the expression levels of OPN in synovial fluid with clinical parameters such as arthroscopic observation of cartilage damage and joint pain after joint injury. METHODS: Synovial fluid was obtained from patients who underwent anterior cruciate ligament (ACL) reconstruction surgery from 2009 through 2011 in our university hospital. The amounts of intact OPN (OPN Full) and it's N-terminal fragment (OPN N-half) in synovial fluid from each patient were quantified by ELISA and compared with clinical parameters such as severity of articular cartilage damage (TMDU cartilage score) and severity of joint pain (Visual Analogue Scale and Lysholm score). RESULTS: Within a month after ACL rupture, both OPN Full and N-half levels in patient synovial fluid were positively correlated with the severity of joint pain. In contrast, patients with ACL injuries greater than one month ago felt less pain if they had higher amounts of OPN N-half in synovial fluid. OPN Full levels were positively correlated with articular cartilage damage in lateral tibial plateau. CONCLUSION: Our data suggest that OPN Full and N-half have distinct functions in articular cartilage homeostasis and in human joint pain.

Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis.

We investigated whether mesenchymal stem cells (MSCs) in synovial fluid (SF) increased in the knee with degenerated cartilage and osteoarthritis. SF was obtained from the knee joints of 22 patients with anterior cruciate ligament (ACL) injury during ACL reconstruction, and cartilage degeneration was evaluated arthroscopically. SF was also obtained from the knee joints of 6 healthy volunteers, 20 patients with mild osteoarthritis, and 26 patients with severe osteoarthritis, in which the grading was evaluated radiographically. The cell component in the SF was cultured for analyses. Synovium (SYN) and bone marrow (BM) were also harvested during total knee arthroplasties. The MSC number in SF was correlated with the cartilage degeneration score evaluated by arthroscopy. The MSC number in the SF was hardly noticed in normal volunteers, but it increased in accordance with the grading of osteoarthritis. Though no significant differences were observed regarding surface epitopes, or differentiation potentials, the morphology and gene profiles in SF MSCs were more similar to those in SYN MSCs than in BM MSCs. We listed 20 genes which were expressed higher in both SYN MSCs and SF MSCs than in BM MSCs, and 3 genes were confirmed by quantitative RT-PCR. MSCs in SF increased along with degenerated cartilage and osteoarthritis.