CARTILAGE-DERIVED MORPHOGENETIC PROTEIN-1

A new morphogenic secreted protein has been identified with direct evi dence for its involvement in skeletal development and joint morphogene sis. Cartilage-derived morphogenetic protein-1 (Cdmp1) and its mouse h omologue growth/differentiation factor 5 (Gdf5) mere discovered indepe ndently using a degenerate PCR screen for bone morphogenetic protein-l ike genes. Cdmp1/Gdf5 belongs to the TGF-beta superfamily, a large gro up of signaling molecules that are secreted as biologically active dim ers with a carboxyl-terminal domain containing seven highly conserved cysteines. Its temporal and spatial expression pattern is mostly restr icted to the developing appendicular skeleton. Genetic studies reveale d that effective null mutations in the gene are associated with short limbs, brachypodism (bp) in mice and acromesomelic chondrodysplasia in humans. Recombinantly expressed protein initiates and promotes chondr ogenesis and to a limited extent osteogenesis in vitro and in vivo. Th is makes this polypeptide a potential therapeutic agent in the regener ation of skeletal tissues. (C) 1997 Elsevier Science Ltd. All rights r eserved.