SUPPRESSED BONE INDUCTION BY FOLLISTATIN IN SPONTANEOUSLY HYPERCHOLESTEROLEMIC RAT BONE

Bone inducing activity in demineralized bone matrix (DBM) of young spo ntaneously hypercholesterolemic (SHC) rats has been shown to be lower than that of aged SHC rats. This study examined the involvement of bon e follistatin, an activin-binding protein, in bone induction. Immunore active follistatin was higher in DBM from IO-week-old SHC rats (DBM-10 wk) than in DBM from 6-month-old SHC rats (DBM-6mo). When DBM without follistatin supplement was implanted, the C-propeptide of type II proc ollagen and calcium contents on day 12 in implants of DBM-6mo were 68% and 40% higher than those of DBM-10wk, respectively. In contrast, fol listatin supplement to DBM decreased C-propeptide of type II procollag en and calcium contents in implants of both DBM-10wk and DBM-6mo, and the levels of these parameters were comparable between DBM-10wk and DB M-6mo, indicating reduced formation of cartilage and bone. These findi ngs suggest that 1) follistatin content in bone matrix decreases with advancing age in SHC rats, and 2) the follistatin interferes with endo chondral bone formation. We demonstrate that the lower bone induction of DBM from young SHC rats was partly due to the abundance of follista tin in bone matrix.