Recombinant human bone morphogenetic protein-2 promotes Indian hedgehog-mediated osteo-chondrogenic differentiation of a human chondrocytic cell line in vivo and in vitro.
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.
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1, Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan. uyama@senzoku.showa-u.ac.jp
Yohei
Y
Uyama
Kimitoshi
K
Yagami
Masashi
M
Hatori
Saburo
S
Kakuta
Masao
M
Nagumo
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology; D024043:Collagen Type II / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D015675:Osteocalcin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta; D015854:Up-Regulation
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin