Intermittent Fugu parathyroid hormone 1 (1–34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats
McManus, Julie F., Davey, Rachel A., MacLean, Helen E., Doust, Elizabeth A., Chiu, W.S. Maria, Sims, Natalie A., Bouxsein, Mary L., Glatt, Vaida, Zajac, Jeffrey D., & Danks, Janine A. (2008) Intermittent Fugu parathyroid hormone 1 (1–34) is an anabolic bone agent in young male rats and osteopenic ovariectomized rats. Bone, 42(6), pp. 1164-1174.
Human parathyroid hormone (hPTH) is currently the only treatment for osteoporosis that forms new bone. Previously we described a fish equivalent, Fugu parathyroid hormone 1 (fPth1) which has hPTH-like biological activity in vitro despite fPth1(1–34) sharing only 53% identity with hPTH(1–34). Here we demonstrate the in vivo actions of fPth1(1–34) on bone. In study 1, young male rats were injected intermittently for 30 days with fPth1 [30 μg–1000 μg/kg body weight (b.w.), (30fPth1–1000fPth1)] or hPTH [30 μg–100 μg/kg b.w. (30hPTH–100hPTH)]. In proximal tibiae at low doses, the fPth1 was positively correlated with trabecular bone volume/total volume (TbBV/TV) while hPTH increased TbBV/TV, trabecular thickness (TbTh) and trabecular number (TbN). 500fPth1 and 1000fPth1 increased TbBV/TV, TbTh, TbN, mineral apposition rate (MAR) and bone formation rate/bone surface (BFR/BS) with a concomitant decrease in osteoclast surface and number. In study 2 ovariectomized (OVX), osteopenic rats and sham operated (SHAM) rats were injected intermittently with 500 μg/kg b.w. of fPth1 (500fPth1) for 11 weeks. 500fPth1 treatment resulted in increased TbBV/TV (151%) and TbTh (96%) in the proximal tibiae due to increased bone formation as assessed by BFR/BS (490%) and MAR (131%). The effect was restoration of TbBV/TV to SHAM levels without any effect on bone resorption. 500fPth1 also increased TbBV/TV and TbTh in the vertebrae (L6) and cortical thickness in the mid-femora increasing bone strength at these sites. fPth1 was similarly effective in SHAM rats. Notwithstanding the low amino acid sequence homology with hPTH (1–34), we have clearly established the efficacy of fPth1 (1–34) as an anabolic bone agent.
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|Item Type:||Journal Article|
|Keywords:||Osteoporosis, Parathyroid hormone, Anabolic, Bone formation, Fish|
|Divisions:||Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
|Copyright Owner:||Copyright 2008 Elsevier Inc.|
|Copyright Statement:||This is the author’s version of a work that was accepted for publication in Bone. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bone, [VOL 42, ISSUE 6, (2008)] DOI: 10.1016/j.bone.2008.01.015|
|Deposited On:||02 May 2014 03:46|
|Last Modified:||06 Jun 2014 05:35|
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