RRC ID 39829
Author Enomoto-Iwamoto M, Nakamura T, Aikawa T, Higuchi Y, Yuasa T, Yamaguchi A, Nohno T, Noji S, Matsuya T, Kurisu K, Koyama E, Pacifici M, Iwamoto M.
Title Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation.
Journal J Bone Miner Res
Abstract Sonic hedgehog (Shh) and Indian hedgehog (Ihh) are important regulators of skeletogenesis, but their roles in this complex multistep process are not fully understood. Recent studies have suggested that the proteins participate in the differentiation of chondrogenic precursor cells into chondrocytes. In the present study, we have tested this possibility more directly. We found that implantation of dermal fibroblasts expressing hedgehog proteins into nude mice induces ectopic cartilage and bone formation. Immunohistological and reverse-transcription polymerase chain reaction (RT-PCR) analyses revealed that the ectopic tissues derived largely if not exclusively from host cells. We found also that treatment of clonal prechondrogenic RMD-1 and ATDC5 cells in culture with Ihh or recombinant amino half of Shh (recombinant N-terminal portion of Shh [rShh-N]) induced their differentiation into chondrocytes, as revealed by cytoarchitectural changes, Alcian blue staining and proteoglycan synthesis. Induction of RMD-1 cell differentiation by Ihh or rShh-N was synergistically enhanced by cotreatment with bone morphogenetic protein 2 (BMP-2) but was blocked by cotreatment with fibroblast growth factor 2 (FGF-2). Our findings indicate that hedgehog proteins have the ability to promote differentiation of chondrogenic precursor cells and that their action in this process can be influenced and modified by synergistic or antagonist cofactors.
Volume 15(9)
Pages 1659-68
Published 2000-9-1
DOI 10.1359/jbmr.2000.15.9.1659
PMID 10976986
MeSH Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins / pharmacology Bone and Bones / drug effects Bone and Bones / embryology Bone and Bones / metabolism Cartilage / cytology Cartilage / drug effects Cartilage / embryology Cartilage / metabolism* Cell Differentiation / drug effects Cell Line Cell Transplantation Chick Embryo Chondrocytes / cytology* Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis* / drug effects Chondrogenesis* / genetics Collagen / genetics Collagen / metabolism Fibroblast Growth Factor 2 / pharmacology Fibroblasts / metabolism Fibroblasts / transplantation Gene Expression Regulation, Developmental / drug effects Hedgehog Proteins Histocytochemistry Mice Mice, Nude Proteins / genetics Proteins / metabolism* Proteins / pharmacology Proteoglycans / biosynthesis RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction / drug effects Trans-Activators* Transfection Transforming Growth Factor beta*
IF 5.854
Times Cited 68
Human and Animal Cells 10T1/2(RCB0247)