Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (11): 1692-1698.doi: 10.12307/2022.353

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Morphological characteristics of subchondral bone in a mouse model of early osteoarthritis

Li Jingyu1, Su Yingying1, Bai Ding2   

  1. 1Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; 2State Key Laboratory of Oral Disease Research, National Oral Disease Clinical Research Center, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2021-04-23 Revised:2021-05-06 Accepted:2021-06-10 Online:2022-04-18 Published:2021-12-11
  • Contact: Bai Ding, MD, Chief physician, State Key Laboratory of Oral Disease Research, National Oral Disease Clinical Research Center, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
  • About author:Li Jingyu, MD, Physician, Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81870804 (to BD)

Abstract: BACKGROUND: Osteoarthritis is a degenerative joint disease, and the main pathological features are cartilage degradation and subchondral bone sclerosis. The function and mechanism of osteocytes in subchondral bone sclerosis remains unclear.
OBJECTIVE: To investigate the pathological characteristics, changes in bone mineralization, morphological changes of osteocytes and expression changes of sclerostin in mice with overloading induced knee osteoarthritis.
METHODS: Twenty 10-week-old male C57BL/6 mice were randomly divided into osteoarthritis group and control group (n=10 per group). Anterior cruciate ligament transection was conducted to establish osteoarthritis models in the osteoarthritis group, and sham operation was carried out in the control group. Four weeks after operations, mice in each group were sacrificed. Knee samples collected were used for hematoxylin-eosin staining, toluidine blue staining and Osteoarthritis Research Society International (OARSI) scoring. Micro-CT was used to evaluate bone mineralization density and bone volume/trabecular volume of subchondral cancellous bone and subchondral lamina dura. Morphological changes of osteocytes and subchondral bone were observed using scanning electron microscope. Immunohistochemistry staining was used to detect SOST/sclerostin expression.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining and toluidine blue staining results showed that significant osteoarthritis phenotype was found in both articular cartilage and subchondral bone in the osteoarthritis group 4 weeks after anterior cruciate ligament transection, accompanied with increased OARSI scores (P < 0.05). Micro-CT scan results showed decreased bone mineralization density and increased bone volume/trabecular volume of subchondral cancellous bone and subchondral lamina dura 4 weeks after anterior cruciate ligament transection (P < 0.05), indicating that subchondral bone sclerosis consists of decreasing of bone mineralization density tissue and increasing of bone volume/trabecular volume. Under the scanning electron microscope, in the osteoarthritis group, normal morphology and arrangement of osteocytes were disturbed in the subchondral bone, while the morphology of mineralization of the subchondral bone was also distorted. Immunohistochemistry staining results showed that, compared with the control group, the number of sclerostin positive cells was significantly decreased in the osteoarthritis group, indicating the morphological changes of osteocytes may be related to changes in SOST/sclerostin expression. In conclusion, subchondral bone sclerosis in early osteoarthritis is mainly manifested as a decrease in bone mineralization density, an increase in bone volume/trabecular volume, and irregular changes in the microscopic morphology of the subchondral bone. After anterior cruciate ligament transection, significant changes in the morphological and arrangement of osteocytes are found in early osteoarthritis, and the secretion of sclerostin is also significantly changed. 

Key words: knee osteoarthritis, subchondral bone, osteocyte, SOST/sclerostin, scanning electron microscope, Micro-CT, bone remodeling

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