1.The pleiotropic role of MEF2C in bone tissue development and metabolism.
Hao-Jie XIAO ; Rui-Qi HUANG ; Sheng-Jie LIN ; Jin-Yang LI ; Xue-Jie YI ; Hai-Ning GAO
Acta Physiologica Sinica 2025;77(2):374-384
The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans
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MEF2 Transcription Factors/physiology*
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Bone and Bones/metabolism*
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Animals
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Bone Development/physiology*
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Osteogenesis/physiology*
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Myogenic Regulatory Factors/physiology*
2.Multi-modal magnetic resonance imaging assessment and mechanism exploration of preterm white matter injury in neonatal rats.
Xiao-Tian GAO ; Hai-Mo ZHANG ; Xiao-Zu ZHANG ; Yi-Jing WANG ; Hui-Ning BI ; Miao YU ; Yan LI ; Xiao-Li WANG
Chinese Journal of Contemporary Pediatrics 2025;27(3):366-372
OBJECTIVES:
To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms.
METHODS:
Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells.
RESULTS:
At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU+PDGFR-α+ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU+Olig2+ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001).
CONCLUSIONS
Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.
Animals
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Rats, Sprague-Dawley
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Magnetic Resonance Imaging/methods*
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Rats
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White Matter/injuries*
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Animals, Newborn
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Female
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Multimodal Imaging
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Male
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Hypoxia-Ischemia, Brain/pathology*
3.Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures (version 2025)
Yong YANG ; Xiaoguang ZHOU ; Qixin CHEN ; Jian CHEN ; Jian DONG ; Liangjie DU ; Shunwu FAN ; Jin FAN ; Zhong FANG ; Haoyu FENG ; Shiqing FENG ; Haishan GUAN ; Aiguo GAO ; Yanzheng GAO ; Yong HAI ; Da HE ; Dengwei HE ; Haiyi HE ; Dianming JIANG ; Xuewen KANG ; Bin LIN ; Baoge LIU ; Changqing LI ; Fang LI ; Li LI ; Fangcai LI ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Xinyu LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Fei LUO ; Yuhai MA ; Keya MAO ; Xuexiao MA ; Bin MENG ; Xu NING ; Limin RONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Dasheng TIAN ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Qingde WANG ; Qinghe WANG ; Lan WEI ; Jigong WU ; Baoshan XU ; Youjia XU ; Guoyong YIN ; Jinglong YAN ; Feng YAN ; Cao YANG ; Huilin YANG ; Qiang YANG ; Bin ZHAO ; Jie ZHAO ; Yue ZHU ; Jianguo ZHANG ; Wenzhi ZHANG ; Zhongmin ZHANG ; Zhaomin ZHENG ; Yan ZENG ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(7):613-626
Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.
4.Effects of combined exposure to dust and noise on blood pressure and electrocardiogram of mechanical manufacturing workers
Rong HAI ; Xiaoping GAO ; Lijie XU ; Xiaoqiao LIANG ; Mengting LIU ; Li NING
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(4):275-280
Objective:To explore the impact of noise and dust exposure in the mechanical manufacturing industry on the risk of hypertension and abnormal electrocardiogram in workers, and their combined effects, in order to provide support for the prevention and treatment of occupational related diseases among workers.Methods:In January 2024, A convenience sampling method was used to study 2802 on-the-job workers who underwent occupational health check-ups from January 2023 to December 2023 at a machinery manufacturing enterprise in Baotou, Inner Mongolia. Blood pressure and electrocardiogram results were analyzed in the noise group, dust group, dust noise group and control group according to the exposure factors. For count data, the chi-square test was employed to analyze differences among groups. Additionally, a binary logistic regression model was utilized to assess the impact of dust and noise exposure on the prevalence of hypertension and electrocardiogram abnormalities.Results:The stratified analysis results showed that the differences in hypertension prevalence among the four groups were statistically significant ( P<0.001) in males, age groups >30-40 years, >40-50 years, >50 years, different exposure durations, and different enterprise sizes. For ECG abnormalities, significant differences were observed among the four groups ( P<0.001) in males, the age group >30-40 years, different enterprise sizes, and those with exposure durations ≤15 years. The trend test for hypertension prevalence across different age groups revealed that as age increased, the prevalence of hypertension showed an upward trend in the noise-exposed group, dust-exposed group, and combined dust-noise-exposed group ( χ2=10.76, 4.25, 6.60, P<0.001, 0.039, 0.010) . Binary regression model analyses revealed that the the risk of hypertension in the noise group, dust group and dust noise group was 2.63 times ( OR=2.63, 95% CI: 1.89~3.67, P<0.001) , 2.36 times ( OR=2.36, 95% CI: 1.76~3.16, P<0.001) and 2.69 times ( OR=2.69, 95% CI: 2.14~3.38, P<0.001) . Using ECG abnormalities as the dependent variable and incorporating the statistically significant variables from Table 1 as independent variables into the binary logistic regression model, the results showed no statistically significant differences in the risk of ECG abnormalities in the dust-exposed, noise-exposed, and combined dust-noise-exposed groups compared to the control group ( P> 0.05) . Conclusion:Combined exposure to dust and noise increases the risk of hypertension in workers and has a combined effect.
5.Effects of combined exposure to dust and noise on blood pressure and electrocardiogram of mechanical manufacturing workers
Rong HAI ; Xiaoping GAO ; Lijie XU ; Xiaoqiao LIANG ; Mengting LIU ; Li NING
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(4):275-280
Objective:To explore the impact of noise and dust exposure in the mechanical manufacturing industry on the risk of hypertension and abnormal electrocardiogram in workers, and their combined effects, in order to provide support for the prevention and treatment of occupational related diseases among workers.Methods:In January 2024, A convenience sampling method was used to study 2802 on-the-job workers who underwent occupational health check-ups from January 2023 to December 2023 at a machinery manufacturing enterprise in Baotou, Inner Mongolia. Blood pressure and electrocardiogram results were analyzed in the noise group, dust group, dust noise group and control group according to the exposure factors. For count data, the chi-square test was employed to analyze differences among groups. Additionally, a binary logistic regression model was utilized to assess the impact of dust and noise exposure on the prevalence of hypertension and electrocardiogram abnormalities.Results:The stratified analysis results showed that the differences in hypertension prevalence among the four groups were statistically significant ( P<0.001) in males, age groups >30-40 years, >40-50 years, >50 years, different exposure durations, and different enterprise sizes. For ECG abnormalities, significant differences were observed among the four groups ( P<0.001) in males, the age group >30-40 years, different enterprise sizes, and those with exposure durations ≤15 years. The trend test for hypertension prevalence across different age groups revealed that as age increased, the prevalence of hypertension showed an upward trend in the noise-exposed group, dust-exposed group, and combined dust-noise-exposed group ( χ2=10.76, 4.25, 6.60, P<0.001, 0.039, 0.010) . Binary regression model analyses revealed that the the risk of hypertension in the noise group, dust group and dust noise group was 2.63 times ( OR=2.63, 95% CI: 1.89~3.67, P<0.001) , 2.36 times ( OR=2.36, 95% CI: 1.76~3.16, P<0.001) and 2.69 times ( OR=2.69, 95% CI: 2.14~3.38, P<0.001) . Using ECG abnormalities as the dependent variable and incorporating the statistically significant variables from Table 1 as independent variables into the binary logistic regression model, the results showed no statistically significant differences in the risk of ECG abnormalities in the dust-exposed, noise-exposed, and combined dust-noise-exposed groups compared to the control group ( P> 0.05) . Conclusion:Combined exposure to dust and noise increases the risk of hypertension in workers and has a combined effect.
6.Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures (version 2025)
Yong YANG ; Xiaoguang ZHOU ; Qixin CHEN ; Jian CHEN ; Jian DONG ; Liangjie DU ; Shunwu FAN ; Jin FAN ; Zhong FANG ; Haoyu FENG ; Shiqing FENG ; Haishan GUAN ; Aiguo GAO ; Yanzheng GAO ; Yong HAI ; Da HE ; Dengwei HE ; Haiyi HE ; Dianming JIANG ; Xuewen KANG ; Bin LIN ; Baoge LIU ; Changqing LI ; Fang LI ; Li LI ; Fangcai LI ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Xinyu LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Xuhua LU ; Fei LUO ; Yuhai MA ; Keya MAO ; Xuexiao MA ; Bin MENG ; Xu NING ; Limin RONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Dasheng TIAN ; Zheng WANG ; Bing WANG ; Linfeng WANG ; Qingde WANG ; Qinghe WANG ; Lan WEI ; Jigong WU ; Baoshan XU ; Youjia XU ; Guoyong YIN ; Jinglong YAN ; Feng YAN ; Cao YANG ; Huilin YANG ; Qiang YANG ; Bin ZHAO ; Jie ZHAO ; Yue ZHU ; Jianguo ZHANG ; Wenzhi ZHANG ; Zhongmin ZHANG ; Zhaomin ZHENG ; Yan ZENG ; Baorong HE ; Wei MEI
Chinese Journal of Trauma 2025;41(7):613-626
Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.
7.Clinical Observation on Abdominal Penetrating Moxibustion Combined with Acupuncture at Four Chong Acupoints for the Treatment of Stroke in the Convalescent Stage
Nan YU ; Jie HU ; Hai-Ning LI ; Shan-Shan SONG ; De-Song ZHENG ; Xin-Hong XUE ; Ying GAO
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):116-122
Objective To observe the effects of abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on balance,walking function and trunk control in patients recovering from stroke.Methods Seventy-eight patients recovering from stroke were randomly divided into an observation group and a control group,with 39 patients in each group.The control group was given conventional rehabilitation exercises,while the observation group was given abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on the basis of the control group.Both groups were treated for 2 consecutive months.After 2 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Berg Scale score and the Timed Up and Go Test(TUGT)were observed before and after treatment.The changes in the National Institutes of Health Stroke Scale(NIHSS)scores were compared before and after treatment between the two groups.The Sheikh Trunk Control Scale scores were also evaluated.Results(1)The total effective rate of the observation group was 94.87%(37/39),and the total effective rate of the control group was 80.00%(31/39),and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).(2)After treatment,the Berg scores of the patients in the two groups were significantly increased(P<0.05),and the Berg scores of the observation group were higher than those of the control group,and the difference was statistically significant(P<0.05).(3)After treatment,the TUGT time and NIHSS score of patients in the two groups were significantly improved(P<0.05),and the TUGT time of the observation group was shorter than that of the control group,and the NIHSS score was lower than that of the control group,and the difference was statistically significant(P<0.05).(4)After treatment,the Sheikh trunk control scores of the two groups were significantly increased(P<0.05),and the Sheikh trunk control score of the observation group was higher than that of the control group,and the difference was statistically significant(P<0.05).Conclusion Abdominal penetrating moxibustion method combined with acupuncture at the four chong points for the treatment of stroke recovery can effectively restore the patients'balance and walking function,improve the patients'trunk control ability,and the therapeutic effect is precise.
8.Reconstructing technology program for heat endurance of soldiers with exertional heat illness(first edition)
Jing-Chun SONG ; Qing SONG ; Bo NING ; Hai-Ling LI ; Yan GAO ; Expert Group of Heatstroke Prevention and Treatment of Chinese PLA
Medical Journal of Chinese People's Liberation Army 2024;49(4):367-370
Officers and soldiers exposed to high temperature and high-humidity environments are highly susceptible to exertional heat illness and even heatstroke.Reports indicated that after conventional treatment,the heat endurance damage in officers/soldiers with exertional heat illness can persist for months or even years.Therefore,the Expert Group of Heatstroke Prevention and Treatment of Heatstroke of Chinese PLA has specially formulated a technical proposal for the reconstruction of heat endurance in officers/soldiers suffering from exertional heatstroke,aiming to provide a safeguard for reconstruction of heat endurance in affected personnel.This article mainly elaborates on the basic concepts,technical requirements,initiation timing,implementation assessment,and follow-up of the heat endurance reconstruction for officers/soldiers with exertional heatstroke.
9.Mechanism of Osteosarcopenia and Its Control by Exercise
Dan JIN ; Xin-Yu DAI ; Miao LIU ; Xue-Jie YI ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(5):1105-1118
Osteosarcopenia (OS) is a multifactorial, multiaetiologic degenerative metabolic syndrome in which sarcopenia coexists with osteoporosis, and its influences are related to aging-induced mechanics, genetics, inflammatory factors, endocrine disorders, and irregular lifestyles. With the accelerated aging process in our country, osteosarcopenia has become a public health problem that cannot be ignored, with a higher risk of falls, fractures, impaired mobility and death. In recent years, scholars at home and abroad have conducted a lot of research on osteosarcopenia, but their pathogenesis is still unclear. Understanding the signaling pathways associated with osteosarcopenia is of great significance for further research on the pathogenesis of these disorders and for finding new targets for treatment. Studies have shown that activation of the PI3K/Akt signaling pathway promotes osteoblast differentiation as well as skeletal muscle regeneration, indicating that inhibition of thePI3K/Akt signaling pathway is closely related to the development of osteosarcopenia. Muscle factor-mechanical stress interactions can maintain osteoblast viability by activating the Wnt/β-catenin signaling pathway, suggesting that Wnt signaling is important in muscle and bone crosstalk. The Notch signaling pathway also plays an important role in improving bone and muscle mass and function, but different researchers hold different views, which need to be further validated and refined in subsequent studies. Exercise, as an existing non-pharmacological treatment with strong and sustained effects on physical function and muscle strength, also significantly increases bone density in osteoporosis patients, which may be mainly due to the fact that exercise induces changes in the form and function of bones, in the form of muscular pulling and indirectly improves the bone mass, and changes in the bone strength can also change the number, shape as well as the function of the muscles. At the same time, the mechanism of different exercise modalities focuses on different aspects, and there are differences in exercise time, exercise intensity, and therapeutic effects in the implementation of interventions. Aerobic exercise can improve the quality of skeletal muscle and increase the expression of osteogenesis-related genes by stimulating mitochondrial biosynthesis, as well as improve the quality and strength of bones and muscles through the Wnt/β- catenin and PI3K/Akt signaling pathways, effectively preventing and controlling the occurrence of musculoskeletal disorders. High-intensity resistance exercise has a significant effect on improving the quality of muscles and bone mineral density, but older people with osteosarcopenia suffer from a decline in muscle quality and strength, and a decline in bone mineral density, which makes them very susceptible to fracture, so they should select the intensity of the training in a gradual and orderly manner, from small to large. What kind of exercise intensity and exercise modalities are most effective in improving the occurrence and development of osteosarcopenia needs to be further investigated. Therefore, this paper mainly reviews the epidemiology of osteosarcopenia, diagnostic criteria, the related signaling pathways (PI3K/Akt pathway, Wnt/β-catenin pathway, Notch pathway, NF-κB pathway) that jointly regulate the metabolic process of myocytes and skeletal cells, as well as the interventional effects of different exercise modes on osteosarcopenia, with the aim of providing theoretical bases for the clinical treatment of osteosarcopenia, as well as enhancing the preventive capacity of the disease in old age.
10.The Role and Possible Mechanisms of Exercise in Combating Osteoporosis by Modulating The Bone Autophagy Pathway
Xin-Yu DAI ; Bin LI ; Dan JIN ; Xue-Jie YI ; Rui-Qi HUANG ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(7):1589-1603
Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

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