INCREASED CARTILAGE AND BONE-FORMATION IN SPONTANEOUSLY HYPERCHOLESTEROLEMIC RATS

Spontaneously hypercholesterolemic (SHC) rats are known to exhibit acc elerated bone resorption. We compared endochondral bone formation indu ced by implantation of demineralized bone matrix (DBM) to 4-week-old S HC rats with that of age-matched Sprague-Dawley (SD) rats. When DBM pr epared from adult SD rats was implanted, the cartilageous area enlarge d, and C-propeptide of type II procollagen content on day 7 was higher in SHC rats. Alkaline phosphatase activity and calcium content on day 12 and tartrate-resistant acid phosphatase activity on day 19 were hi gher in SHC rats. These results suggest active chondrogenesis, with a subsequent increase in osteogenesis, and stimulated osteoclastic bone resorption in SHC rats. When DBM from 10-week-old SHC rats was implant ed into SD or SHC rats, the levels of bone forming parameters on day 1 2 were reduced to one-third, suggesting inhibiting factor(s) for bone induction in bone matrix of SHC rats. In contrast, when DBM from 6-mon th-old SHC rats was implanted, although bone forming parameters in SD rats were comparable to the case of implantation of DBM from SD rats, the accelerated bone formation detected in SHC rats was blocked, indic ating resistance to systemic bone inducing factor(s) of SHC rats in ag ed bone matrix. These results suggest that age-related decrease in res ponses to some systemic bone inducing factor may lead to the bone loss with advancing age.