Biotinated bone morphogenetic protein-2: In vivo and in vitro activity

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was biotinated, an d the bioactivity of biotinated protein was assessed in vitro (alkaline pho sphate induction in limb bud cells) and in vivo (osteoinduction in the rat ectopic assay). Amino-biotinated rhBMP-2 exhibited an increase in bioactivi ty whereas carboxy-biotinated rhBMP-2 did not exhibit any changes in bioact ivity in vitro. Avidin inhibited the bioactivity of amino-biotinated but no t carboxyl-biotinated rhBMP-2. Both amino- and carboxy-modified rhBMP-2 ind uced bone at an equivalent level to that of unmodified rhBMP-2 in vivo. The presence of avidin did not affect the osteoinductive activity of both type s of biotinated rhBMP-2. The overall results indicated that binding to a la rge protein, avidin, might affect rhBMP-2 activity in vitro depending on th e binding site; however, in vivo activity was unaffected by the avidin bind ing. (C) 1999 John Wiley & Sons, Inc.