Crucial Role of Calcitonin Gene-related Peptide in Biodegradable Magnesium-enhanced Bone Fracture Healing in Ovariectomised Rats
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AbstractPoorly healing bone fractures resulting from trauma or osteoporosis remain a major clinical challenge. Orthopaedic implants containing biodegradable magnesium (Mg), an essential element in the bone matrix, have been used for fracture repair with considerable efficacy; however, the underlying mechanisms remain largelyunknown. Here we report that abundant new bone was formed around the peripheral cortex of cortical bone after intramedullary implantation of an ultrapure magnesium-containing rod in rat femur, accompanied by significant increase in expression of calcitonin gene-related peptide (CGRP), a sensory neuropeptide important for osteogensis. The magnesium-induced osteogenic effect could be significantly reversed by surgical removal of the periosteum, sensory nerve denervation via injection of high-does capsaicin, or by shRNA-based knockdown of encoding calcitonin receptor-like receptor (CRLR) or receptor activity-midifying protein 1 (RAMP1; encoding, the binding site for CGRP). In contrast, a substantially enhanced osteogenic effect was induced by overexpression of CRLR or RAMP1 in the rat femur. In the isolated dorsal root ganglion neurons, the elevation of extracellular Mg2+-induced MagT1- and TRPM7-dependent Mg2+ entry, intracellular ATP increase, and synaptic vesicles accumulation at axon terminals. Knockdown of CRLR or RAMP1 in periosteum-derived stem cells also significantly reduced CGRP-induced osteogenic differentiation. We have further demonstrated significantly enhanced fracture repair by an innovative Mg-containing intramedullary nail in an ovariectomised-induced osteoporosis rat model. Together, a previously undefined role of Mg in promoting CGRP-mediated osteogenic differentiation is revealed, explaining this ion's therapeutic potential in orthopaedics.
All Author(s) ListJK Xu, JL Wang, KKW Ho, PSH Yung, KM Chan, L Qin
Name of ConferenceThe Hong Kong Orthopaedic Association 36th Annual congress
Start Date of Conference05/11/2016
End Date of Conference06/05/2017
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Year2016
Pages29 - 29
LanguagesEnglish-United States

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