GRK 2154 - Materials for Brain

GRK colloquium talk by Prof. Ling Qin: The Role of Magnesium Ions in Bone Fracture Repair via Neuronal Regulation

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology & Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing, Institute of Health Sciences. The Chinese University of Hong Kong, PR China

Jun 07, 2018 from 05:00 PM to 06:00 PM

TF Aquarium

Abstract:

Bone fracture repair resulting from trauma or osteoporosis remain a major clinical challenge. Orthopedic implants containing biodegradable magnesium (Mg), an essential element in the bone matrix, have been used for fracture repair with considerable efficacy reported by our group and others; however, the underlying cellular and molecular mechanisms by which Mg promotes bone formation remain largely unknown. We investigated abundant new bone formation occurred around the peripheral cortex of cortical bone after intramedullary implan-tation of an ultrapure Mg-containing rod in rat femur, accompanied by significant increase in expression of calcitonin gene-related peptide (CGRP), a sensory neuropeptide important for osteogenesis. The Mg-induced osteogenic effect can be significantly reduced by surgical removal of the periosteum, sensory nerve denervation via injection of capsaicin, or by shRNA-based knockdown of Calcrl (encoding calcitonin receptor-like receptor). In contrast, a substantially enhanced osteogenic effect is induced by overexpression of Calcrl in the rat femur. In the isolated rat dorsal root ganglion neurons, the elevation of extracellular Mg2+ induces MagT1- and TRPM7-dependent Mg2+-entry, intracellular ATP increase and vacuo-lar-ATPase-involved aggregation of synaptic vesicles at axon terminals. Knockdown of Calcrl in periosteum-derived stem cells also significantly reduces the CGRP-increased osteogenic differentiation markers. We have also observed significant enhancement of fracture repair by an innovative Mg-containing intramedullary nail in an ovariectomy-induced osteoporosis rat model. Taken together, our results suggest that implant-derived Mg2+ is able to promote bone fracture healing by inducing local neuronal production of CGRP and indicate the therapeutic potentials of biodegradable Mg implants for orthopedic applications. Now we extended to designing endogenous and exogenous CGRP delivery system for osteoporotic fracture and critical bone defect repair for potential clinical transla-tion. 
Acknowledgement: The relevant studies are fully supported by Theme-based Research Scheme (Ref. T13-402/17-N) and Collaborative Research Fund (Ref. C4028-14G, C4026-17W) of the Research Grants Council of the Hong Kong Special Administrative Region, PR China.
 

Regine Willumeit-Römer

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