title: BMP5 activates multiple signaling pathways and promotes chondrogenic differentiation in the ATDC5 growth plate model.
abstract: The bone morphogenetic protein 5 (BMP5) participates in skeletal development but its direct effects on the function of growth plate chondrocytes during chondrogenesis have not been explored. We have investigated the signaling pathways activated by BMP5 and its effect on chondrogenic differentiation in the ATDC5 growth plate chondrocyte model. BMP5 transiently activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase signaling after 10 days of differentiation; sustained Smad and p38 MAPK signaling were seen after 15 days differentiation. All three pathways were activated by BMP5 in human adult articular chondrocytes. BMP5 alone and in combination with the chondrogenic enhancer, insulin, induced proteoglycan synthesis, aggrecan core protein 1 expression, and alkaline phosphatase activity. Upregulation of hypertrophic markers parathyroid receptor 1 and collagen type X alpha 1 occurred in BMP5-treated ATDC5 cultures. BMP5 is clearly chondrogenic and exhibits stage-specific regulation of multiple signaling pathways in this growth plate model. In particular, BMP5 accelerates expression of hypertrophy markers which is of relevance in both development and diseases such as osteoarthritis.
authors.affiliation: School of Biological Sciences, Biomedical Research Centre, University of East Anglia, Norwich, NR4 7TJ, UK. sarah.snelling@ndorms.ox.ac.uk
authors.forename: Sarah J B
authors.initials: SJ
authors.lastname: Snelling
authors.forename: Philippa A
authors.initials: PA
authors.lastname: Hulley
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
mesh_terms: D000328:Adult; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D001846:Bone Development / Q000502:physiology*; D055417:Bone Morphogenetic Protein 5 / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020219:Chondrogenesis / Q000187:drug effects; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006132:Growth Plate / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D055417:Bone Morphogenetic Protein 5; D007328:Insulin; D011509:Proteoglycans; D044168:Receptor, Parathyroid Hormone, Type 1; D051785:Smad Proteins; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase