Endochondral ossification signals in cartilage degradation during osteoarthritis progression in experimental mouse models

• Published in: Molecules and cells Vol. 25; no. 1; pp. 1 - 6
• Main Author: Kawaguchi, Hiroshi (University of Tokyo, Tokyo, Japan), E-mail: kawaguchi-ort@h.u-tokyo.ac.jp
• Format: Journal Article
• Language: English
• Published: United States 한국분자세포생물학회 29.02.2008
• Subjects: Animals; APOPTOSE; APOPTOSIS; CARTILAGE; Cartilage, Articular - cytology; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; CARTILAGO; Cell Communication - physiology; chondrocytes; Chondrocytes - cytology; Chondrocytes - metabolism; Chondrocytes - pathology; Collagen Type X - metabolism; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Disease Models, Animal; Disease Progression; endochondral ossification; ENFERMEDADES DE LAS ARTICULACIONES; HIPERTROFIA; Humans; HYPERTROPHIE; HYPERTROPHY; JOINT DISEASES; MALADIE DES ARTICULATIONS; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 13 - metabolism; Mice; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteoarthritis - physiopathology; Osteogenesis - physiology; Peptide Hydrolases - metabolism; Stress, Mechanical; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1016/s1016-8478(23)17544-3

Osteoarthritis (OA), one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have, been developed to apply approaches from mouse genetics. Although proteinases like matrix metalloproteinases and aggrecanases have now been proven to be the principal initiators of OA progression, clinical trials of proteinase inhibitors have not been successful for the treatment, turning the interest of researchers to the upstream signals of proteinase induction. These signals include undegraded and fragmented matrix proteins like type Ⅱ collagen or fibronection that affects chondrocytes through distinct receptors. Another signal is proinflammatory factors that are produced by chondrocytes and synovial cells; however, recent studies that used mouse OA models in knockout mice did not support that these factors have a role in the central contribution to OA development. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease.