High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling

Abstract

Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.

Resorbable Mg2+-Containing Phosphates for Bone Tissue Repair

“…It can also significantly increase the expression of β-catenin and its downstream genes (LEF1 and DKK1), which, in turn, forces hBMSC to differentiate into the direction of the osteoblast lineage and causes an osteogenic effect. In addition, Hamushan et al [42] reported that the magnesium cations enhance the consolidation in distraction osteogenesis through regulation of the PTCH protein by activating the Hedgehog (Hh) signal transduction pathway, which is an alternative Wnt signaling pathway. Magnesium derived from implants improves the treatment of fractures in rats by promoting the neurological fabrication of CGRP (calcitonin-associated peptide) [43,44].…”

Research progress on the hedgehog signalling pathway in regulating bone formation and homeostasis

“…Thus, Hh‐alternative Wnt signalling co‐worked in the distraction osteogenesis process and could be regulated to enhance bone formation. 73 GRK2 was identified as an essential regulator of skeletogenesis, and mutations in GRK2 could lead to skeletal ciliopathies by impairing both Hh signalling and Wnt signalling. 74 Tang et al examined the effect of lithium chloride (LiCl) on the differentiation of BMMSCs and identified that LiCl markedly accelerated cell osteogenic differentiation and inhibited adipogenic differentiation simultaneously.…”

Resorbable Mg²⁺-Containing Phosphates for Bone Tissue Repair

“…It also can significantly increase the expression of β-catenin and it`s downstream genes (LEF1, DKK1), which, in turn, forces hBMSC to differentiate into the direction of the osteoblast lineage and causes an osteogenic effect. Also, Hamushan et al [41] reported that the magnesium cations are enhancing the consolidation in distraction osteogenesis through regulation of PTCH protein by activating the Hedgehog (Hh) signal transduction pathway. That is an alternative Wnt signaling pathway.…”