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Regulation of Hedgehog signaling Offers A Novel Perspective for Bone Homeostasis Disorder Treatment

College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, Inner Mongolia, China
Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou 075131, Hebei, China
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(16), 3981;
Received: 7 July 2019 / Revised: 10 August 2019 / Accepted: 14 August 2019 / Published: 16 August 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
The hedgehog (HH) signaling pathway is central to the regulation of bone development and homeostasis. HH signaling is not only involved in osteoblast differentiation from bone marrow mesenchymal stem cells (BM-MSCs), but also acts upstream within osteoblasts via the OPG/RANK/RANKL axis to control the expression of RANKL. HH signaling has been found to up-regulate parathyroid hormone related protein (PTHrP) expression in osteoblasts, which in turn activates its downstream targets nuclear factor of activated T cells (NFAT) and cAMP responsive element binding protein (CREB), and as a result CREB and NFAT cooperatively increase RANKL expression and osteoclastogenesis. Osteoblasts must remain in balance with osteoclasts in order to avoid excessive bone formation or resorption, thereby maintaining bone homeostasis. This review systemically summarizes the mechanisms whereby HH signaling induces osteoblast development and controls RANKL expression through PTHrP in osteoblasts. Proper targeting of HH signaling may offer a therapeutic option for treating bone homeostasis disorders. View Full-Text
Keywords: hedgehog; RANKL; osteoblast; PTHrP; CREB; NFAT hedgehog; RANKL; osteoblast; PTHrP; CREB; NFAT
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Lv, W.-T.; Du, D.-H.; Gao, R.-J.; Yu, C.-W.; Jia, Y.; Jia, Z.-F.; Wang, C.-J. Regulation of Hedgehog signaling Offers A Novel Perspective for Bone Homeostasis Disorder Treatment. Int. J. Mol. Sci. 2019, 20, 3981.

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