title: BMP-5 expression increases during chondrocyte differentiation in vivo and in vitro and promotes proliferation and cartilage matrix synthesis in primary chondrocyte cultures.
abstract: Bone morphogenetic proteins (BMPs) play pivotal roles in bone and cartilage growth and repair. Through phenotypes of short-ear (se) mice, which have BMP-5 mutations, a role for BMP-5 in some specific aspects of skeletogenesis and cartilage growth is known. This report examines BMP-5 expression in the growth plate and in differentiating cultures of primary chondrocytes, and the effects of addition of BMP-5 or its inhibition by anti-BMP-5 antibody in chondrocyte cultures. By laser capture microdissection and immunohistochemistry, we found that BMP-5 is expressed in proliferating zone (PZ) chondrocytes and that the expression increases sharply with hypertrophic differentiation. A similar pattern was observed in differentiating cultures of primary chondrocytes, with BMP-5 expression increasing as cells differentiated, in contrast to other BMPs. BMP-5 added to cultures increased cell proliferation early in the culture period and also stimulated cartilage matrix synthesis. Also, BMP-5 addition to the cultures activated phosphorylation of Smad 1/5/8 and p38 MAP kinase and caused increased nuclear accumulation of phospho-Smads. Anti-BMP-5 antibody inhibited the endogenous BMP-5, reducing cell proliferation and phospho-Smad nuclear accumulation. Together, the results demonstrate that BMP-5 is normally an important regulator of chondrocyte proliferation and differentiation. Whether other BMPs may compensate in BMP-5 loss-of-function mutations is discussed.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, USA.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Mailhot
authors.forename: Meiheng
authors.initials: M
authors.lastname: Yang
authors.forename: April
authors.initials: A
authors.lastname: Mason-Savas
authors.forename: Carole A
authors.initials: CA
authors.lastname: Mackay
authors.forename: Irwin
authors.initials: I
authors.lastname: Leav
authors.forename: Paul R
authors.initials: PR
authors.lastname: Odgren
mesh_terms: D000818:Animals; D055417:Bone Morphogenetic Protein 5; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000502:physiology; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000032:analysis; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051381:Rats; D012272:Ribs / Q000166:cytology
chemical_list: C525815:Bmp5 protein, mouse; D055417:Bone Morphogenetic Protein 5; D019485:Bone Morphogenetic Proteins; D006025:Glycosaminoglycans