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. 2010 Jan 4;120(2):582–592. doi: 10.1172/JCI40568

Figure 6. mOSM stimulates RANKL via OSMR yet inhibits sclerostin via LIFR and stimulates bone formation in Osmr–/– mice.

Figure 6

(A and B) Fold changes in Rankl and Sost mRNA levels in primary calvarial osteoblasts 6 hours after commencing treatment with mLIF, hOSM, or mOSM (all 2 ng/ml) with and without 1 hour pretreatment with 2.5 μg/ml LA. Mean ± SEM of 3 independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001 vs. vehicle-treated cells of the same genotype and antagonist exposure. (C) Phosphorylation of WT and Osmr–/– osteoblasts stimulated with mLIF, hOSM, or mOSM (each 50 ng/ml). pSTAT1/STAT1 (90 kDa), pSTAT3/STAT3 (86 kDa), pSTAT5/STAT5 (90 kDa) detected between 98 kDa and 62 kDa molecular weight markers (left side of figure). pERK/ERK (42/44 kDa) and pan-actin (42 kDa) were detected between 49 kDa and 38 kDa. The pSTAT3/STAT3 Western blot is from 1 film, but it has been spliced to maintain a consistent order within the figure. pSTAT1/STAT1 and pERK/ERK were probed sequentially on the same gel. (D) hOSM and mOSM (both 2 ng/ml) injected over calvariae of Osmr–/– mice (n = 5–6/group) increased calvarial thickness (Cv.Th.) without increasing MS/BS, but increased MAR, and hOSM increased BFR/BS compared with saline-treated controls. *P < 0.05; **P < 0.01, vs. saline-treated control. (E) A model of mOSM action. OSM, produced by osteoblasts, osteocytes, and bone-lining cells acts through OSMR in osteoblasts and their precursors to promote osteoblast differentiation and inhibit adipocyte differentiation as well as stimulating osteoclast differentiation by increasing RANKL expression. In contrast, in the osteocyte, mOSM acts through LIFR in osteocytes to inhibit sclerostin, an osteocyte-specific inhibitor of mineralization, thus modifying bone formation independently of effects on osteoclast and adipocyte differentiation.