Meijome, Tomas E.Baughman, Jenna T.Hooker, R. AdamCheng, Ying-HuaCiovacco, Wendy A.Balamohan, Sanjeev M.Srinivasan, Trishya L.Chitteti, Brahmananda R.Eleniste, Pierre P.Horowitz, Mark C.Srour, Edward F.Bruzzaniti, AngelaFuchs, Robyn K.Kacena, Melissa A.2020-02-062020-02-062016-04Meijome, T. E., Baughman, J. T., Hooker, R. A., Cheng, Y. H., Ciovacco, W. A., Balamohan, S. M., … Kacena, M. A. (2016). C-Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis. Journal of cellular biochemistry, 117(4), 959–969. doi:10.1002/jcb.25380https://hdl.handle.net/1805/21997C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c-Mpl was globally knocked out (c-Mpl(-/-) mice) would have decreased bone mass because they have fewer MKs. Instead, c-Mpl(-/-) mice have a higher bone mass than WT controls. Using c-Mpl(-/-) mice we investigated the basis for this discrepancy and discovered that c-Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c-Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c-Mpl deficiency results in a net gain in bone volume with increases in OBs and OCs. In vitro, a higher percentage of c-Mpl(-/-) OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real-time PCR and functional assays. In co-culture systems, which allow for the interaction between OBs and OC progenitors, c-Mpl(-/-) OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2-EphB2/B4, were unaffected in c-Mpl(-/-) OBs. These data provide new findings for the role of MKs and c-Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis.en-USPublisher PolicyThrombopoietinc-MplOsteoblastsOsteoclastsBone massArticle