Mechanisms of synovial joint and articular cartilage development

Abstract

Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal elements develop from transient cartilage by a biological process known as endochondral ossification. Accumulating evidence indicates that articular and growth plate cartilage are derived from different cell sources and that different molecules and signaling pathways regulate these two kinds of cartilage. As the first sign of joint development, the interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, joint cavitation occurs in the center of the interzone, and the cells in the interzone and its surroundings gradually form articular cartilage and the synovial joint. During joint development, the interzone cells continuously migrate out to the epiphyseal cartilage and the surrounding cells influx into the joint region. These complicated phenomena are regulated by various molecules and signaling pathways, including GDF5, Wnt, IHH, PTHrP, BMP, TGF-β, and FGF. Here, we summarize current literature and discuss the molecular mechanisms underlying joint formation and articular development.

Keywords: Articular cartilage; Chondrocyte; Interzone; Joint.

Fig. 1

Joint formation and articular cartilage development in the early stage. The interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, joint cavitation occurs in the center of the interzone, and the cells in the interzone and its surroundings gradually form articular cartilage and synovial joints. During joint development, the interzone cells continuously migrate to the epiphyseal cartilage and the surrounding cells influx into the joint region. The width of each box indicates the area, where a particular molecule is expressed. GDF5 growth differentiation factor 5, BMP bone morphogenetic protein, Ihh Indian hedgehog, FGFR fibroblast growth factor receptor, TGF-β transforming growth factor-β, MAPK mitogen-activated protein kinase, UDPGD uridine diphosphoglucose dehydrogenase, HA hyaluronic acid, PTHrP parathyroid hormone-related protein, PRG4 proteoglycan 4, Col2a1 type II collagen, (+) positive, (−) negative