Abstract
We examined osteo-chondrogenic differentiation of a human chondrocytic cell line (USAC) by rhBMP-2 in vivo and in vitro. USAC was established from a transplanted tumor to athymic mouse derived from an osteogenic sarcoma of the mandible. USAC usually shows chondrocytic phenotypes in vivo and in vitro. rhBMP-2 up-regulated not only the mRNA expression of types II and X collagen, but also the mRNA expression of osteocalcin and Cbfa1 in USAC cells in vitro. In vivo experimental cartilaginous tissue formation was prominent in the chamber with rhBMP-2 when compared with the chamber without rhBMP-2. USAC cells implanted with rhBMP-2 often formed osteoid-like tissues surrounded by osteoblastic cells positive for type I collagen. rhBMP up-regulated Ihh, and the expression of Ihh was well correlated with osteo-chondrogenic cell differentiation. These results suggest that rhBMP-2 promotes chondrogenesis and also induces osteogenic differentiation of USAC cells in vivo and in vitro through up-regulation of Ihh.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / pharmacology*
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Bone Morphogenetic Proteins / physiology
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Cell Differentiation / drug effects*
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Cell Differentiation / physiology
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Cell Division / drug effects
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Cell Line
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Chondrocytes / cytology*
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Chondrocytes / drug effects
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Chondrocytes / metabolism
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Chondrogenesis / physiology
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Collagen Type II / drug effects
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Collagen Type II / genetics
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Collagen Type II / metabolism
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Collagen Type X / drug effects
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Collagen Type X / genetics
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Collagen Type X / metabolism
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Core Binding Factor Alpha 1 Subunit
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Hedgehog Proteins
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Humans
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Mice
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Neoplasm Proteins / drug effects
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Osteoblasts / cytology
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Osteoblasts / physiology
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Osteocalcin / drug effects
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Osteocalcin / genetics
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Osteocalcin / metabolism
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Osteogenesis / physiology
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RNA, Messenger / drug effects
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Recombinant Proteins / pharmacology
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Trans-Activators / drug effects
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Trans-Activators / metabolism*
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Transcription Factors / drug effects
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transforming Growth Factor beta*
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Up-Regulation
Substances
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BMP2 protein, human
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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Collagen Type II
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Collagen Type X
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Core Binding Factor Alpha 1 Subunit
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Hedgehog Proteins
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Neoplasm Proteins
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RNA, Messenger
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Recombinant Proteins
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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recombinant human bone morphogenetic protein-2
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Osteocalcin