The role of connective tissue growth factor in skeletal growth and development.

Connective tissue growth factor (CTGF) is a secreted, extracellular matrix-associated protein that regulates diverse cellular functions in different cell types. CTGF gene belongs to a larger CCN gene family that also includes Cyr61 and NOV. It modulates many cellular functions, including proliferation, migration, adhesion, and extracellular matrix production, and it is involved in many biological and pathological processes. CTGF has special importance in skeletal development. During Meckel's cartilage development, CTGF acts as a down-stream molecule of TGFbeta to stimulate cell-cell interactions and the expression of condensation-associated genes. CTGF promotes endochondral ossification and articular cartilage regeneration. During the healing of experimental bone fracture, CTGF was expressed in periosteal cells and hypertrophic chondrocytes. It promotes the proliferation of chondrocytes and osteoblasts. CTGF is a down-stream mediator for prostaglandin E2 (PGE2) in osteoblast-induced proliferation. It also regulates signaling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). Constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation.