Leukemia inhibitory factor is mitogenic to osteoblasts

Leukemia inhibitory factor (LIF) regulates cell growth and is produced by a variety of tissues, including bone. Previously we have shown that recombinant human LIF induced an increase in osteoclast number, bone formation, and DNA synthesis. In the present study, we have defined the cells in intact bone at which the proliferative effects of LIF occur, using simultaneous enzyme histochemistry and autoradiographic techniques. The area of alkaline phosphatase-positive staining was increased twofold (p = 0.0008) and the number of [3H]thymidine-positive cells was increased two-fold (p = 0.0024) in LIF-treated bones. The radiolabeled cells either calocalized with alkaline phosphatase or were in the osteoprogenitor region. They were not found in the acid phosphatase-positive staining osteoclasts. These results indicate that cells which have a mitogenic response to LIF are bone-forming rather than bone-resorbing cells.