Growth factor regulation of human growth plate chondrocyte proliferation in vitro.
Linear growth occurs as the result of growth plate chondrocytes undergoing proliferative and hypertrophic phases. Paracrine feedback loops that regulate the entry of chondrocytes into the hypertrophic phase have been shown and similar pathways likely exist for the proliferative phase. Human long-bone growth plate chondrocytes were cultured in vitro. The proliferative effects of a variety of factors were determined by [3H]thymidine uptake and the gene expression profile of these cells was determined by DNA microarray analysis. Serum, insulin-like growth factor (IGF)-I and -II, transforming growth factor-beta (TGF-beta, fibroblast growth factor (FGF)-1, -2, and -18, and platelet-derived growth factor (PDGF)-BB were potent stimulators of proliferation. FGF-10, testosterone, and bone morphogenetic proteins (BMP)-2, -4, and -6 inhibited proliferation. Microarray analysis showed that the genes for multiple members of the IGF-I, TGF-beta, FGF, and BMP pathways were expressed, suggesting the presence of autocrine/paracrine pathways that regulate the proliferative phase of growth plate-mediated growth.
Olney
Robert C
RC
Cellular and Molecular Medicine Laboratory, The Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA. rolney@nemours.org
Wang
Jianwei
J
Sylvester
James E
JE
Mougey
Edward B
EB
D000293:Adolescent; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005312:Fetal Blood; D020869:Gene Expression Profiling; D006132:Growth Plate / Q000166:cytology*; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008297:Male; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000096:biosynthesis; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism
D006133:Growth Substances; D006728:Hormones; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D003094:Collagen; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D013936:Thymidine