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- Title
Endogenous Parathyroid Hormone Promotes Fracture Healing by Increasing Expression of BMPR2 through cAMP/PKA/CREB Pathway in Mice.
- Authors
Zhou, Wei; Yu, Lipeng; Fan, Jin; Wan, Bowen; Jiang, Tao; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Hu, Zhaoxing
- Abstract
Background/Aims: Endogenous parathyroid hormone (PTH) plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP) and/or the transforming growth factor-β (TGF-β) signaling pathway. Methods: Eight-week-old wild-type (WT) and PTH-knockout (PTH KO) male mice were selected, and models of open right-femoral fracture were constructed. Fracture healing and callus characteristics of mice in the two groups were compared by X-ray, microcomputed tomography, histological, and immunohistochemical examinations. Bone marrow mesenchymal stem cells (BMMSCs) of 8-week-old WT and PTHKO male mice were obtained and induced into osteoblasts and chondrocytes. Results: We found that expression levels of Runt-related transcription factor (RUNX2), bone morphogenetic protein-receptor-type II (BMPR2), phosphorylated Smad 1/5/8, and phosphorylated cyclic adenosine monophosphateresponsive element binding protein (CREB) in the callus of PTHKO mice were significantly decreased, whereas no significant difference in expression of SOX9, TGF-βR2,or pSMAD2/3 was observed between PTHKO and WT mice. Additionally, the activity of osteoblast alkaline phosphatase was low at 7 days post-induction, and was upregulated by addition of PTH or dibutyryl cyclic adenosine monophosphate (dbcAMP) to the cell culture. Furthermore, H89 (protein kinase A inhibitor)eliminated the simulating effects of PTH and dbcAMP, and a low concentration of cyclic adenosine monophosphate (cAMP) was observed in PTHKO mouse BMMSCs. Conclusion: These results suggested that endogenous PTH enhanced BMPR2 expression by a cAMP/PKA/CREB pathway in osteoblasts, and increased RUNX2 expression through transduction of the BMP/pSMAD1/5/8 signaling pathway.
- Subjects
PARATHYROID hormone; FRACTURE healing; BONE morphogenetic proteins; CREB protein; TRANSFORMING growth factors-beta; RUNX proteins; CELLULAR signal transduction; LABORATORY mice
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2017, Vol 42, Issue 2, p551
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000477605