1. Academic Validation
  2. hPTH(3-34)(29-34) selectively activated PKC and mimicked osteoanabolic effects of hPTH(1-34)

hPTH(3-34)(29-34) selectively activated PKC and mimicked osteoanabolic effects of hPTH(1-34)

  • Bone. 2020 Jun;135:115326. doi: 10.1016/j.bone.2020.115326.
Youhua He 1 Minghan Li 1 Guojun Tong 1 Yue Meng 1 Song Hao 1 Shaoyu Hu 1 Wenjuan Yan 2 Dehong Yang 3
Affiliations

Affiliations

  • 1 Department of Orthopedics-Spine Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • 2 Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: 645613053@qq.com.
  • 3 Department of Orthopedics-Spine Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: drmyang@yahoo.com.
Abstract

Teriparatide (hPTH(1-34)) exhibits both osteoanabolic and osteocatabolic effects. We generated a novel PTH analog by duplicating the PTH(29-34) domain to hPTH(3-34) (named MY-1), which was identified to activate PKC but not PLC and cAMP/PKA signaling. It increased osteo-differentiation but did not affect osteoclastogenesis and RANKL expression in primary osteoblasts or bone marrow cells. MY-1 and hPTH(1-34) increased the synthesis and decreased the degradation οf β-catenin protein in osteoblasts, while PKC Inhibitor blunted such effects. In vivo results indicated that intermittent MY-1 and hPTH(1-34) prevented bone loss in ovariectomized mice, and that MY-1 infusion increased bone volume in normal mice. Histological analysis observed more osteoclasts surrounding the cancellous bone surface in hPTH(1-34), but not MY-1 treated mice. We conclude that MY-1 mimicked the osteoanabolic but not the osteocatabolic effects of hPTH(1-34), which is related to PKC and β-catenin signaling. Such anabolic-only analog provides a new strategy to study PTH's versatile functions and design new medicines to treat osteoporosis and bone defects.

Keywords

Osteo-differentiation; Osteoporosis; Parathyroid hormone; Peptide engineering; Protein kinase C.

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