LACK OF BONE-RESORPTION IN OSTEOSCLEROTIC (OC OC) MICE IS DUE TO A DEFECT IN OSTEOCLAST PROGENITORS RATHER THAN THE LOCAL MICROENVIRONMENT PROVIDED BY OSTEOBLASTIC CELLS

In a co-culture system of mouse spleen cells and osteoblastic cells, we have demonstrated that a suitable microenvironment must be provided by osteoblastic cells in order for osteoclast-like multinucleated cell (MNC) formation. Using this co-culture system, we examined the pathogenetic mechanism underlying the lack of bone resorption in osteosclerotic oc oc mice. Numerous tartrate-resistant acid phosphatase (TRAP, an osteoclast marker enzyme)-positive MNCs were formed in response to 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] both in co-cultures of oc oc spleen cells and normal osteoblastic cells and in those of normal spleen cells and oc oc osteoblastic cells. TRAP-positive MNCs derived from normal spleen cells tended to spread out on culture dishes, whereas those from oc oc spleen cells remained as small, compact MNCs. When TRAP-positive MNCs enriched from co-cultures of normal spleen cells and oc oc osteoblastic cells were cultured on dentine slices, they formed numerous resorption pits with ruffled borders and clear zones. In contrast, none of the TRAP-positive MNCs derived from oc oc spleen cells formed either ruffled borders or resorption pits. These results indicate that the lack of bone resorption in oc oc mice is due to a defect in osteoclast progenitors rather than the local microenvironment provided by osteoblastic cells. © 1992.