Abstract
Osteoclast inhibitory lectin (OCIL) is a recently identified inhibitor of osteoclast formation. A variety of osteotropic factors regulate OCIL expression in osteoblastic cells, however, little information is available to date concerning how this gene is controlled. Using real-time RT-PCR, we examined the regulation of OCIL expression by PTHrp and the signaling pathways used. We demonstrated in rat osteoblast-like UMR-106 cells, rat calvarial primary osteoblastic cells, and murine MC3T3-E1 cells, PTHrp(1–34) increased OCIL expression. In UMR-106 cells, the increase began and reached maximum later than RANKL induction and OPG suppression. cAMP/PKA signaling activators PTH(1–31), forskolin and dibutyryl cAMP (db-cAMP), and calcium ionophore A23187 all increased OCIL levels. In contrast, PKC activator phorbol-12-myristate-13-acetate reduced OCIL expression in short term but induced OCIL mRNA in long term. PKA inhibitor KT5720, mitogen-activated protein kinase (MAPK) cascade inhibitor PD98059, calmodulin antagonist W-7, and Ca2+/calmodulin-dependent protein kinase II (CaMK II) inhibitor KN-62 all significantly blunted PTHrp-stimulated OCIL expression. Moreover, PD98059 blocked the stimulation of OCIL by FSK or db-cAMP but not that by A23187. In primarily cultured osteoblasts, the PTHrp induction of OCIL was blocked by KT5720, W-7, and PD98059 as well. The data established that PTHrp(1–34) regulates OCIL expression in vitro through cAMP/PKA, Ca2+/CaMK II, and MAPK signaling pathways.
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This work was supported by a project of Natural Science Foundation of China (No. 30300171), a project of Tianjin Municipal Natural Science Foundation (No. 07JCZDJC07500), a project of Tianjin Education Commission (No. 20050230), and a key project of Chinese Ministry of Education (No. 208011).
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Fang Zheng and Hui Liang contributed equally to this work.
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Zheng, F., Liang, H., Liu, R. et al. Parathyroid hormone-related protein regulates osteoclast inhibitory lectin expression via multiple signaling pathways in osteoblast-like cells. Endocr 35, 47–56 (2009). https://doi.org/10.1007/s12020-008-9118-2
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DOI: https://doi.org/10.1007/s12020-008-9118-2