Osteocyte- specific dentin matrix protein 1

Aims There is an increasing concern of osteoporotic fractures in the ageing population. Low -magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteo-porotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. Methods A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments in-cluded radiography, micro -CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte- Y4 (MLO- Y4) osteocyte- like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocy-tochemistry on osteocyte-specific markers as above, and mineralized nodule staining. Results Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD sig-nificantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. Conclusion The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhance-ment on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing.

Automated summary

This study investigated the role of osteocyte-specific DMP1 in osteoporotic fracture healing augmented by low-magnitude high-frequency vibration (LMHFV). The results showed that blocking DMP1 would impair healing outcomes and negate the enhancement of fracture healing induced by LMHFV. These findings reveal the importance of DMP1 in response to mechanical signals during osteoporotic fracture healing.