title: The small leucine-rich proteoglycan biglycan modulates BMP-4-induced osteoblast differentiation.
abstract: 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.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. xchen@dir.nidr.nih.gov
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
authors.forename: Larry W
authors.initials: LW
authors.lastname: Fisher
authors.forename: Pamela Gehron
authors.initials: PG
authors.lastname: Robey
authors.forename: Marian F
authors.initials: MF
authors.lastname: Young
mesh_terms: D000818:Animals; D058578:Biglycan; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D006801:Humans; D007930:Leucine / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: C546884:BGN protein, human; C525809:BMP4 protein, human; C546885:Bgn protein, mouse; D058578:Biglycan; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D014157:Transcription Factors; D007930:Leucine; D002118:Calcium