Lin Chen1,2,3,4, Shao Cheng1,2,3, Kanghui Sun1,2,3, Jing Wang1,2,3, Xinhua Liu5, Yongjian Zhao1,2,3, Junjie Yang1,2,3, Dongfeng Zhao1,2,3, Chunchun Xue1,2,3,4, Yuren Tao1,2,3, Shitian Zhao1,2,3, Hao Zhang1,2,3, Sheng Lu1,2,3, Qi Shi1,2,3, Yongjun Wang1,2,3, Bing Shu6,7,8. 1. Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. 2. Spine Institute, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200032, China. 3. Key Laboratory, Ministry of Education of China, Shanghai, 200032, China. 4. Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 5. Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 6. Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. siren17721101@163.com. 7. Spine Institute, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 200032, China. siren17721101@163.com. 8. Key Laboratory, Ministry of Education of China, Shanghai, 200032, China. siren17721101@163.com.
Abstract
BACKGROUND: Macrophages and inflammatory cytokines play important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture healing under the condition of postmenopausal osteoporosis have not been fully revealed. METHODS: Tibia transverse fracture was established 12 weeks after ovariectomy or sham operation in 16-week old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28 days after fracture for radiological and histological examinations. M1/M2 inflammatory macrophages, osteal macrophages and gene expressions of tumor necrosis factor-α, interleukin-6, interleukin-1β and macrophage conversion related molecules in the fracture haematoma or callus were also detected. RESULTS: The processes of fracture healing, especially the phases of endochondral ossification and callus remodeling, were delayed in ovariectomized mice. The expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-1β, in the fracture haematoma or callus were disturbed. Expressions of tumor necrosis factor-α were decreased at 1, 14 and 21 days post-fracture (DPF), and were increased at 3, 5 and 7 DPF. Interleukin-6 expressions at 1, 3 and 21 DPF were significantly increased. We found the decreases in M1 and M2 macrophages at 1 DPF of the initial inflammatory stage. M2 macrophages at 14 DPF of the middle stage and osteal macrophages at 14, 21 and 28 DPF of the middle and late stages of fracture healing were also reduced in ovariectomized mice. CONCLUSIONS: The expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.
BACKGROUND: Macrophages and inflammatory cytokines play important roles in bone fracture healing. However, the expression patterns of macrophages and inflammatory cytokines during fracture healing under the condition of postmenopausal osteoporosis have not been fully revealed. METHODS: Tibia transverse fracture was established 12 weeks after ovariectomy or sham operation in 16-week old female mice. Tibias were harvested before fracture or 1, 3, 5, 7, 14, 21, 28 days after fracture for radiological and histological examinations. M1/M2 inflammatory macrophages, osteal macrophages and gene expressions of tumor necrosis factor-α, interleukin-6, interleukin-1β and macrophage conversion related molecules in the fracture haematoma or callus were also detected. RESULTS: The processes of fracture healing, especially the phases of endochondral ossification and callus remodeling, were delayed in ovariectomized mice. The expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-1β, in the fracture haematoma or callus were disturbed. Expressions of tumor necrosis factor-α were decreased at 1, 14 and 21 days post-fracture (DPF), and were increased at 3, 5 and 7 DPF. Interleukin-6 expressions at 1, 3 and 21 DPF were significantly increased. We found the decreases in M1 and M2 macrophages at 1 DPF of the initial inflammatory stage. M2 macrophages at 14 DPF of the middle stage and osteal macrophages at 14, 21 and 28 DPF of the middle and late stages of fracture healing were also reduced in ovariectomized mice. CONCLUSIONS: The expressions of macrophages and inflammatory cytokines were impaired in ovariectomized mice, which might contribute partially to poor fracture healing.
Authors: Kylie A Alexander; Ming K Chang; Erin R Maylin; Thomas Kohler; Ralph Müller; Andy C Wu; Nico Van Rooijen; Matthew J Sweet; David A Hume; Liza J Raggatt; Allison R Pettit Journal: J Bone Miner Res Date: 2011-07 Impact factor: 6.741
Authors: W Lehmann; C M Edgar; K Wang; T-J Cho; G L Barnes; S Kakar; D T Graves; J M Rueger; L C Gerstenfeld; T A Einhorn Journal: Bone Date: 2005-02 Impact factor: 4.398
Authors: Louis C Gerstenfeld; Dennis M Cullinane; George L Barnes; Dana T Graves; Thomas A Einhorn Journal: J Cell Biochem Date: 2003-04-01 Impact factor: 4.429
Authors: Xu Yang; Benjamin F Ricciardi; Alexia Hernandez-Soria; Yuexian Shi; Nancy Pleshko Camacho; Mathias P G Bostrom Journal: Bone Date: 2007-08-15 Impact factor: 4.398
Authors: Daigo Hashimoto; Andrew Chow; Clara Noizat; Pearline Teo; Mary Beth Beasley; Marylene Leboeuf; Christian D Becker; Peter See; Jeremy Price; Daniel Lucas; Melanie Greter; Arthur Mortha; Scott W Boyer; E Camilla Forsberg; Masato Tanaka; Nico van Rooijen; Adolfo García-Sastre; E Richard Stanley; Florent Ginhoux; Paul S Frenette; Miriam Merad Journal: Immunity Date: 2013-04-18 Impact factor: 31.745
Authors: Ming K Chang; Liza-Jane Raggatt; Kylie A Alexander; Julia S Kuliwaba; Nicola L Fazzalari; Kate Schroder; Erin R Maylin; Vera M Ripoll; David A Hume; Allison R Pettit Journal: J Immunol Date: 2008-07-15 Impact factor: 5.422
Authors: Liza J Raggatt; Martin E Wullschleger; Kylie A Alexander; Andy C K Wu; Susan M Millard; Simranpreet Kaur; Michelle L Maugham; Laura S Gregory; Roland Steck; Allison R Pettit Journal: Am J Pathol Date: 2014-10-05 Impact factor: 4.307
Authors: Zhengmeng Yang; Lu Feng; Ming Wang; Yucong Li; Shanshan Bai; Xuan Lu; Haixing Wang; Xiaoting Zhang; Yaofeng Wang; Sien Lin; Micky D Tortorella; Gang Li Journal: Nutrients Date: 2022-05-18 Impact factor: 6.706