Objective: In this study, we aimed to explore the role of MicroRNA-26 in photobiomodulation (PBM)- and adipose-derived stem cell (ADS)-based healing of critical-sized foot fractures in a rat model. Background: PBM and ADS treatments are relatively invasive methods for treating bone defects. Specific and oriented cellular and molecular functions can be induced by applying an appropriate type of PBM and ADS treatment. Methods: A critical size foot defect (CSFD) is induced in femoral bones of 24 rats. Then, a human demineralized bone matrix scaffold (hDBMS) was engrafted into all CSFDs. The rats were randomly allocated into four groups (n = 6): (1) control (hDBMS); (2) hDBMS+human ADSs (hADSs), hADSs engrafted into CSFDs; (3) hDBMS+PBM, CSFD exposed to PBM (810 nm wavelength, 1.2 J/cm2 energy density); and (4) hDBMS+(hADSs+PBM), hADSs implanted into the CSFD and then exposed to PBM. At 42 days after CSFD induction, the rats were killed, and the left CSFD was removed for mechanical compression tests and the right CSFD was removed for molecular and histological studies. Results: The results indicate that miRNA-26a, BMP, SMAD, RUNX, and OSTREX had higher expression in the treated groups than in the control group. Further, the biomechanical and histological properties of CSFDs in treated groups were improved compared with the control group. Correlation tests revealed a positive relationship between microRNA and improved biomechanical and cellular parameters of CSFDs in the rat model. Conclusions: We concluded that the MicroRNA-26 signaling pathway probably plays a significant role in the hADS-, PBM-, and hADS+PBM-based healing of CSFDs in rats. Clinical Trial Registration number: IR.SBMU.MSP.REC.1398.980.
Keywords: MicroRNA-26; adipose-derived stem cell; critical size foot defect; osteogenic genes; photobiomodulation.