OSTEOADHERIN, A CELL-BINDING KERATAN SULFATE PROTEOGLYCAN IN BONE, BELONGS TO THE FAMILY OF LEUCINE-RICH REPEAT PROTEINS OF THE EXTRACELLULAR-MATRIX

Osteoadherin is a recently described bone proteoglycan containing kera tan sulfate. It promotes integrin (alpha(v)beta(3))-mediated cell bind ing (Wendel, M., Sommarin, Y., and Heinegard, D. (1998) J. Cell Biol. 141, 839-847). The primary structure of bovine osteoadherin has now be en determined by nucleotide sequencing of a cDNA clone from a primary bovine osteoblast expression library. The entire translated primary se quence corresponds to a 49,116-Da protein with a calculated isoelectri c point for the mature protein of 5.2. The dominating feature is a cen tral region.consisting of 11 B-type, leucine-rich repeats ranging in l ength from 20 to 30 residues. The full, primary sequence contains four putative sites for tyrosine sulfation, three of which are at the N-te rminal end of the molecule. There are six potential sites for N-linked glycosylation present, Osteoadherin shows highest sequence identity, 42%, to bovine keratocan and 31-38% identity to bovine fibromodulin, l umican, and human PRELP. Unique to osteoadherin is the presence of a l arge and very acidic C-terminal domain. The distribution of cysteine r esidues resembles that of other leucine-rich repeat proteins except fo r two centrally located cysteines. Northern blot analysis of RNA sampl es from various bovine tissues showed a 4.5-kilobase pair message for osteoadherin to be expressed in bone only. Osteoadherin mRNA was detec ted by in situ hybridization in mature osteoblasts located superficial ly on trabecular bone.