Osteocyte-specific dentin matrix protein 1: the role of mineralization regulation in low-magnitude high-frequency vibration enhanced osteoporotic fracture healing

Bone & Joint Research

article

Meng C. M. Li¹  Simon K-H. Chow¹  Ronald M. Y. Wong¹  Bailing Chen²  Jack C. Y. Cheng¹  Ling Qin¹  Wing-Hoi Cheung¹ 

[1] Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong;Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University

关键词: Osteocyte;    Dentin matrix protein 1;    Osteoporotic fracture healing;    Vibration;    matrix protein;    Fracture healing;    staining;    mice models;    osteoporotic fracture healing;    vibration treatment;    long bone;    metaphyseal fracture;    distal femur;   

DOI  :  10.1302/2046-3758.117.BJR-2021-0476.R2

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsThere 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.MethodsA 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.ResultsHealing 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.ConclusionThe 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.

【 授权许可】

CC BY-NC