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

Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA

¹Correspondence: Bldg. 30, Room 225, National Institute of Dental and Craniofacial Research, National Institutes of Health, 9000 Rockville Pike, MSC 4320, Bethesda, MD 20892, USA. E-mail: xchen{at}dir.nidr.nih.gov

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 bgn-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 bgn-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)

Key Words: microenvironment • osteoblastic progenitors

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