Colony-stimulating factor 1 when combined with parathyroid hormone or 1,25-dihydroxyvitamin D can produce osteoclasts in cultured neonatal metatarsals from toothless (tl-osteopetrotic) rats.

Toothless (tl-osteopetrotic) rats have little or no endogenous bone resorption, no marrow spaces, and very few osteoclasts and macrophages, and their live metatarsal rudiments cannot support the development of normal osteoclasts in vitro. The recent demonstration that exogenous colony-stimulating factor 1 (CSF-1) improves skeletal sclerosis and increases osteoclasts in tl rats in vivo, prompted us to explore conditions that enable osteoclasts to be formed in tl metatarsals in vitro. Coculture of neonatal tl metatarsals with CSF-1 alone produced no osteoclasts, but the addition of normal spleen and bone marrow cells and parathyroid hormone or 1,25-dihydroxyvitamin D produced osteoclasts in most cultures. Identical cultures of metatarsals from the CSF-1 deficient op/op mouse produced similar results. Within the contexts of the role of CSF-1 in osteoclastogenesis and the different biologic manifestations of osteopetrosis in these two mutations, we interpret these results to mean that other factors are required to restore osteoclast function completely in tl rats and op mice. Thus, experimental studies of these mutations are likely to provide new insights on both osteopetrosis and osteoclast biology.