gp130 in late osteoblasts and osteocytes is required for PTH-induced osteoblast differentiation

    1. Natalie A Sims1,2
    1. 1St.Vincent's Institute of Medical Research, 9 Princes St, Fitzroy, Victoria 3065, Australia
      2Department of Medicine at St. Vincent's Hospital Melbourne, The University of Melbourne, Fitzroy, Victoria, Australia
      3Department of Cancer Research and Molecular Medicine, The KG Jebsen Center for Myeloma Research and Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
    1. Correspondence should be addressed to N A Sims; Email: nsims{at}


    Parathyroid hormone (PTH) treatment stimulates osteoblast differentiation and bone formation, and is the only currently approved anabolic therapy for osteoporosis. In cells of the osteoblast lineage, PTH also stimulates the expression of members of the interleukin 6 (IL-6) cytokine superfamily. Although the similarity of gene targets regulated by these cytokines and PTH suggest cooperative action, the dependence of PTH anabolic action on IL-6 cytokine signaling is unknown. To determine whether cytokine signaling in the osteocyte through glycoprotein 130 (gp130), the common IL-6 superfamily receptor subunit, is required for PTH anabolic action, male mice with conditional gp130 deletion in osteocytes (Dmp1Cre.gp130f/f) and littermate controls (Dmp1Cre.gp130w/w) were treated with hPTH(1–34) (30 μg/kg 5× per week for 5 weeks). PTH dramatically increased bone formation in Dmp1Cre.gp130w/w mice, as indicated by elevated osteoblast number, osteoid surface, mineralizing surface, and increased serum N-terminal propeptide of type 1 collagen (P1NP). However, in mice with Dmp1Cre-directed deletion of gp130, PTH treatment changed none of these parameters. Impaired PTH anabolic action was associated with a 50% reduction in Pth1r mRNA levels in Dmp1Cre.gp130f/f femora compared with Dmp1Cre.gp130w/w. Furthermore, lentiviral-Cre infection of gp130f/f primary osteoblasts also lowered Pth1r mRNA levels to 16% of that observed in infected C57/BL6 cells. In conclusion, osteocytic gp130 is required to maintain PTH1R expression in the osteoblast lineage, and for the stimulation of osteoblast differentiation that occurs in response to PTH.

    • Received in final form 19 August 2014
    • Accepted 15 September 2014
    • Made available online as an Accepted Preprint 16 September 2014
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    1. J Endocrinol 223 181-190
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