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.
MeSH terms
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Animals
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Biglycan
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins / metabolism
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Bone Morphogenetic Proteins / pharmacology*
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Calcium / metabolism
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Cell Differentiation / drug effects*
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Cells, Cultured
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Core Binding Factor Alpha 1 Subunit
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Decorin
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Extracellular Matrix Proteins
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Gene Expression Regulation
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Humans
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Leucine / metabolism*
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Mice
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Mice, Inbred C3H
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Mice, Knockout
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Neoplasm Proteins / metabolism
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Osteoblasts / cytology
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Osteoblasts / drug effects*
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Osteoblasts / metabolism
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Protein Binding
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Proteoglycans / chemistry*
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Proteoglycans / deficiency
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Proteoglycans / genetics
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Proteoglycans / metabolism*
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Signal Transduction / drug effects
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Skull / cytology
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Skull / metabolism
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Transcription Factors / metabolism
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Transcriptional Activation
Substances
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BGN protein, human
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BMP4 protein, human
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Bgn protein, mouse
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Biglycan
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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Core Binding Factor Alpha 1 Subunit
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DCN protein, human
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Dcn protein, mouse
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Decorin
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Extracellular Matrix Proteins
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Neoplasm Proteins
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Proteoglycans
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Transcription Factors
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Leucine
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Calcium