The small leucine‐rich proteoglycan biglycan modulates BMP‐4‐induced osteoblast differentiation

Biglycan (bgn) is a small leucine‐rich proteoglycan enriched in extracellular matrices of skeletal tissues. Bgn ‐deficient mice develop age‐related osteopenia with a phenotype that resembles osteoporosis and premature arthritis. In the present study, we have examined the differentiation of ftgw‐deficient osteoblasts from neonatal murine calvariae and found that the absence of bgn caused less BMP‐4 binding, which reduced the sensitivity of osteoblasts to BMP‐4 stimulation. The loss of sensitivity resulted in a reduction of Cbfa1 expression, which ultimately led to a defect in the differentiation of osteoblasts. However, the response of ftgw‐deficient osteoblasts to BMP‐4 was completely rescued by reintroduction of biglycan by viral transfection. We propose that biglycan modulates BMP‐4‐induced signaling to control osteoblast differentiation.—Chen, X.‐D., Fisher, L. W., Robey, P. G., Young, M. F. The small leucine‐rich proteoglycan biglycan modulates BMP‐4‐induced osteoblast differentiation. FASEB J. 18, 948–958 (2004)