Abstract
Parathyroid hormone (PTH) has biphasic effects on bone: continuous treatment is catabolic whereas intermittent treatment is anabolic. The mechanism(s) responsible for these differing effects are still unclear, partly because of the previous nonβavailability of a model system in which effects on both formation and resorption indices could be studied concomitantly. In cultured marrow cells from 6βweek old C57BL/6 mice, we demonstrated that 4 days of intermittent PTH treatment increased mRNA for osteoblast differentiation markers (Runx2, alkaline phosphatase (AP), and type I procollagen (COL1A1) whereas continuous treatment resulted in production of large numbers of TRAPβpositive multinucleated osteoclasts. Although IGFβI mRNA did not increase after intermittent treatment, it was consistently higher than after continuous treatment, and the addition of an antiβIGFβI neutralizing antibody prevented the increase in bone formation indices observed with intermittent treatment. By contrast, after continuous treatment, gene expression of RANK ligand (RANKL) was increased and that of osteoprotegerin (OPG) was decreased, resulting in a 25βfold increase in the RANKL/OPG ratio. In this model system, the data suggest that intermittent PTH treatment enhances osteoblast differentiation through an IGFβI dependent mechanism and continuous PTH treatment enhances osteoclastogenesis through reciprocal increases in RANKL and decreases in OPG. J. Cell. Biochem. 89: 180β190, 2003. Β© 2003 WileyβLiss, Inc.