Decoding Cold Therapy Mechanisms of Enhanced Bone Repair through Sensory Receptors and Molecular Pathways

Author:

Zakaria Matthew1ORCID,Matta Justin1,Honjol Yazan1,Schupbach Drew12,Mwale Fackson3,Harvey Edward12ORCID,Merle Geraldine14ORCID

Affiliation:

1. Surgical and Interventional Sciences Division, Faculty of Medicine, McGill University, Montreal, QC H3A 2B2, Canada

2. Department of Surgery, Faculty of Medicine, McGill University, Montreal, QC H3A 0C5, Canada

3. Lady Davis Institute for Medical Research, Lady Davies Institute Jewish General Hospital, 3755 Cote-St. Catherine Road, Room 602, Montréal, QC H3T 1E2, Canada

4. Department of Chemical Engineering, École Polytechnique de Montréal, Montreal, QC H3T 1J4, Canada

Abstract

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with the physiological responses analyzed. Vasoconstriction was mediated by an increase in the transient receptor protein channels (TRPs), transient receptor potential ankyrin 1 (TRPA1; p = 0.012), and transient receptor potential melastatin 8 (TRPM8; p < 0.001), within cortical defects, enhancing the sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p < 0.01) and vascular endothelial growth factor expression (VEGF; p < 0.001), promoting angiogenesis, vital for bone regeneration. The increased expression of osteogenic proteins peroxisome proliferator-activated receptor gamma coactivator (PGC-1α; p = 0.039) and RNA-binding motif protein 3 (RBM3; p < 0.008) suggests that the reparative processes have been stimulated. Enhanced osteoblast differentiation and the presence of alkaline phosphatase (ALP) at day 5 (three-fold, p = 0.021) and 10 (two-fold, p < 0.001) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.019), indicating the presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy’s multifaceted effects on bone repair, offering insights for therapeutic strategies.

Funder

Merle

NSERC discovery

FRQS chercheur boursier J1

Publisher

MDPI AG

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