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Bone

Neuronal origin of osteogenic effects of magnesium

Fracture-fixation implants made of biodegradable materials are highly desirable, especially those whose degradation products are safe and enhance fracture healing. “Magnesium (Mg) is such an ideal material and, additionally, is an essential component of our bone matrix,” explains Ling Qin, lead investigator of a new study published in Nature Medicine, which shows that Mg-induced osteogenesis is mediated by local neuronal production of calcitonin gene-related peptide 1 (CGRP1).

Surgical implantation of a pure Mg rod into the medullary cavity of intact rat femurs induced substantially more new bone formation and a greater total bone volume than a stainless steel rod 2 weeks after the procedure. Moreover, removal of the periosteum at the time of implantation prevented Mg-induced formation of new bone, as did capsaicin-mediated destruction of sensory neurons within the periosteum. As Mg-induced formation of new bone was associated with increased levels of CGRP1 in peripheral cortical bone and dorsal root ganglia neurons, the team investigated the effect of overexpression or knockdown of the gene encoding the CGRP1 receptor (Calcrl). Whereas overexpression of Calcrl enhanced Mg-induced formation of new bone, knockdown had the opposite effect. The involvement of CGRP1 in Mg-induced osteogenesis was confirmed by showing that CGRP1 promoted osteogenic differentiation of isolated periosteum-derived stem cells.

“We have identified a previously undefined role of Mg in promoting CGRP1-mediated osteogenic differentiation,” comments Qin. “Cell-specific and tissue-specific targeting systems that can deliver Mg or osteogenic proteins to fracture sites have great potential to facilitate and enhance fracture healing, and could assist early initiation of mobility and rehabilitation of patients with fractures.”

References

  1. Zhang, Y. et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat. Med. http://dx.doi.org/10.1038/nm.4162 (2016)

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Holmes, D. Neuronal origin of osteogenic effects of magnesium. Nat Rev Endocrinol 12, 687 (2016). https://doi.org/10.1038/nrendo.2016.160

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  • DOI: https://doi.org/10.1038/nrendo.2016.160

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