Best5: a novel interferon-inducible gene expressed during bone formation

Regulation of bone formation is important in the pathogenesis of many condi tions such as osteoporosis, fracture healing, and loosening of orthopedic i mplants. We have recently identified a novel rat cDNA (best5) by differenti al display PCR that is regulated during osteoblast differentiation and bone formation in vitro and in vivo, Expression of best5 mRNA is induced in cul tures of osteoblasts by both interferon-alpha (IFN-alpha) or IFN-gamma. Whe reas IFN-alpha induced a rapid, transient induction of best5 expression pea king at 4-6 h poststimulation, IFN-gamma elicited a more prolonged inductio n of best5 expression, which remained elevated 48 h poststimulation, A poly clonal antibody generated to a peptide derived from the best5 coding region recognized a 27 kDa protein on Western blot analysis of osteoblast lysates . We localized BEST5 protein in osteoblast progenitor cells and mature oste oblasts in sections of rat tibiae and in sections of bones loaded in vivo t o induce adaptive bone formation. Best5 may therefore be a fundamental inte rmediate in the response of osteoblasts to stimuli that modulate proliferat ion/ differentiation, such as interferons or mechanical loading. These find ings highlight the close interactions between the immune system and bone ce lls and may open new therapeutic avenues in modulating bone mass.