PMID- 35787000 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220816 IS - 2046-3758 (Print) IS - 2046-3758 (Electronic) IS - 2046-3758 (Linking) VI - 11 IP - 7 DP - 2022 Jul TI - Osteocyte-specific dentin matrix protein 1 : the role of mineralization regulation in low-magnitude high-frequency vibration enhanced osteoporotic fracture healing. PG - 465-476 LID - 10.1302/2046-3758.117.BJR-2021-0476.R2 [doi] AB - AIMS: There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic 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 included 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 immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. RESULTS: Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly 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 enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465-476. FAU - Li, Meng C M AU - Li MCM AUID- ORCID: 0000-0001-8720-2008 AD - Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. FAU - Chow, Simon K-H AU - Chow SK AUID- ORCID: 0000-0003-1742-980X AD - Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. FAU - Wong, Ronald M Y AU - Wong RMY AUID- ORCID: 0000-0001-5615-6627 AD - Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. FAU - Chen, Bailing AU - Chen B AD - Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. FAU - Cheng, Jack C Y AU - Cheng JCY AUID- ORCID: 0000-0001-8153-364X AD - Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. FAU - Qin, Ling AU - Qin L AUID- ORCID: 0000-0001-6173-6167 AD - Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. FAU - Cheung, Wing-Hoi AU - Cheung WH AUID- ORCID: 0000-0003-3247-8255 AD - Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China. LA - eng PT - Journal Article PL - England TA - Bone Joint Res JT - Bone & joint research JID - 101586057 PMC - PMC9350691 OTO - NOTNLM OT - Dentin matrix protein 1 OT - Fracture healing OT - Osteocyte OT - Osteoporotic fracture healing OT - Vibration OT - distal femur OT - long bone OT - matrix protein OT - metaphyseal fracture OT - mice models OT - osteoporotic fracture healing OT - staining OT - vibration treatment EDAT- 2022/07/06 06:00 MHDA- 2022/07/06 06:01 PMCR- 2022/07/13 CRDT- 2022/07/05 17:07 PHST- 2022/07/05 17:07 [entrez] PHST- 2022/07/06 06:00 [pubmed] PHST- 2022/07/06 06:01 [medline] PHST- 2022/07/13 00:00 [pmc-release] AID - BJR-11-465 [pii] AID - 10.1302/2046-3758.117.BJR-2021-0476.R2 [doi] PST - ppublish SO - Bone Joint Res. 2022 Jul;11(7):465-476. doi: 10.1302/2046-3758.117.BJR-2021-0476.R2.