Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis

Dai, Bingyang; Xu, Jiankun; Li, Xu; Huang, Le; Hopkins, Chelsea; Wang, Honglian; Yao, Hao; Mi, Jie; Zheng, Lizhen; Wang, Jiali; Tong, Wenxue; Chow, Dick Ho Kiu; Li, Ye; He, Xuan; Hu, Ping; Chen, Ziyi; Zu, Haiyue; Li, Yixuan; Yao, Yao; Jiang, Qing; Qin, Ling

doi:10.1038/s41467-021-27683-w

Cited by 40 publications

(35 citation statements)

References 62 publications

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“…Patients with sarcopenia hiding in the normal BMI population were the confounding factor that created a false impression of the “obesity paradox”; therefore, BF% might be a better indicator for obesity diagnosis in old people. From the current results, the “obesity paradox” did not exist in old people with obesity defined by BF%, which was consistent with basic science studies and underlying molecular mechanisms ( 11 ). From the odds ratio results, sarcopenia is more associated with age-related osteoporosis than obesity, which emphasized the role of muscle in osteoporosis ( 46 ).…”

Section: Discussionsupporting

confidence: 91%

“…However, when body composition of fat and lean mass is taken into consideration, body fat mass is negatively associated with BMD in the younger population, while lean mass plays a positive role ( 10 ). In animal models, diet-induced obesity impairs bone turnover through cytokines and osteopontin secreted by adipose tissues, which activate osteoclasts and accelerate bone degradation ( 11 ). On the other hand, strain induced by muscle contraction stimulates bone growth as osteoblasts are mechanosensitive ( 6 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

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Muscle plays a more superior role than fat in bone homeostasis: A cross-sectional study of old Asian people

et al. 2023

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ObjectivesThe aim of this study was to discover the role of fat and muscle in bone structures, as well as the relationship between obesity and sarcopenia on age-related osteoporosis.MethodsA total of 400 participants (65.0 ± 8.2 years old, 42.3% women) were recruited. Fat, muscle, bone parameters, basic demographics, medical history, physical performance and activity, and calcium intake of participants were obtained from datasets. The diagnosis of osteoporosis, sarcopenia, and obesity was based on current recommendations. Pearson correlation, non-linear regression models, and decision tree analyses were performed to study the relationship between fat, muscle, and bone. Logistic regression analyses were used to explore the risk of osteoporosis in old people with obesity or sarcopenia via Model 1 (unadjusted) and Model 2 (adjusted by age, physical activity, and calcium intake).ResultsCorrelation analysis showed that limb muscle mass and index, and age were best related to bone mineral density (BMD) (|r| = 0.386–0.632, p < 0.001). On the contrary, body mass index (BMI) and increased body fat percentage (BF%) were harmful for bone health. An increase of BMI and fat mass index slowed the increase of BMD in the spine, while skeletal muscle mass index accelerated the increase. People with sarcopenia had low muscle mass and strength. When separating subjects into sarcopenia and non-sarcopenia status, sarcopenia was independently related to higher risks of osteoporosis in both models (OR > 1, p < 0.05). BMI-defined obesity in Model 1 as well as BF%-defined obesity in both models did not reduce the risk of osteoporosis in both models (p > 0.05). The decision tree classification (85% accuracy) showed that greater body weight and larger lower limb muscle performance were negatively related to osteoporosis, while fat mass and percentage did not play roles in this prediction.ConclusionLow muscle mass and function were harmful to bone health. Obesity defined by both BMI and BF% had limited protective roles in osteoporosis. The benefits for bone from increased muscle mass and function play a more superior role than increased fat mass in old people. Sarcopenia prevention and treatment instead of controlling obesity should be recommended as an approach to reduce the risks of age-related osteoporosis and fragility fracture for elderly people.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Muscle plays a more superior role than fat in bone homeostasis: A cross-sectional study of old Asian people

et al. 2023

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“…Dai et al. ( 39 ) found that OPN secreted by the macrophages in epididymal white adipose tissue regulated the bone metabolism in high-fat diet (HFD)-induced obesity. The OPN selectively circulated to the bone marrow and promoted the degradation of the bone matrix by activating osteoclasts, both surgical removal of epididymal white adipose tissue and local injection of OPN-neutralizing antibodies or drugs aimed to deplete macrophages could ameliorate HFD-induced bone loss in mice.…”

Section: The Structure and Function Of Opnmentioning

confidence: 99%

Osteopontin, a bridge links osteoarthritis and osteoporosis

Bai

Li²,

Zhang³

2022

Front. Endocrinol.

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Osteoarthritis (OA) is the most prevalent joint disease characterized by degradation of articular cartilage, inflammation, and changes in periarticular and subchondral bone of joints. Osteoporosis (OP) is another systemic skeletal disease characterized by low bone mass and bone mineral density (BMD) accompanied by microarchitectural deterioration in bone tissue and increased bone fragility and fracture risk. Both OA and OP are mainly affected on the elderly people. Recent studies have shown that osteopontin (OPN) plays a vital role in bone metabolism and homeostasis. OPN involves these biological activities through participating in the proliferation, migration, differentiation, and adhesion of several bone-related cells, including chondrocytes, synoviocytes, osteoclasts, osteoblasts, and marrow mesenchymal stem cells (MSCs). OPN has been demonstrated to be closely related to the occurrence and development of many bone-related diseases, such as OA and OP. This review summarizes the role of OPN in regulating inflammation activity and bone metabolism in OA and OP. Furthermore, some drugs that targeted OPN to treat OA and OP are also summarized in the review. However, the complex mechanism of OPN in regulating OA and OP is not fully elucidated, which drives us to explore the depth effect of OPN on these two bone diseases.

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“…Macrophages also promote the synthetic effects of parathyroid hormone (PTH), a key regulatory hormone of bone homeostasis, in bone tissue [ 154 , 155 ]. Macrophages in white adipose tissue are involved in the secretion of osteopontin, which may be a potential pathway for the treatment of obesity-associated bone disease [ 156 ]. Thus, macrophages may further coordinate bone homeostasis through the macrophage-osteoblast axis.…”

Section: Effect Of the Macrophage–osteoblast Axis On Bone Homeostasismentioning

confidence: 99%

Strategies of Macrophages to Maintain Bone Homeostasis and Promote Bone Repair: A Narrative Review

Huang

Chen

et al. 2022

JFB

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Bone homeostasis (a healthy bone mass) is regulated by maintaining a delicate balance between bone resorption and bone formation. The regulation of physiological bone remodeling by a complex system that involves multiple cells in the skeleton is closely related to bone homeostasis. Loss of bone mass or repair of bone is always accompanied by changes in bone homeostasis. However, due to the complexity of bone homeostasis, we are currently unable to identify all the mechanisms that affect bone homeostasis. To date, bone macrophages have been considered a third cellular component in addition to osteogenic spectrum cells and osteoclasts. As confirmed by co-culture models or in vivo experiments, polarized or unpolarized macrophages interact with multiple components within the bone to ensure bone homeostasis. Different macrophage phenotypes are prone to resorption and formation of bone differently. This review comprehensively summarizes the mechanisms by which macrophages regulate bone homeostasis and concludes that macrophages can control bone homeostasis from osteoclasts, mesenchymal cells, osteoblasts, osteocytes, and the blood/vasculature system. The elaboration of these mechanisms in this narrative review facilitates the development of macrophage-based strategies for the treatment of bone metabolic diseases and bone defects.

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Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis

Cited by 40 publications

References 62 publications

Muscle plays a more superior role than fat in bone homeostasis: A cross-sectional study of old Asian people

Muscle plays a more superior role than fat in bone homeostasis: A cross-sectional study of old Asian people

Osteopontin, a bridge links osteoarthritis and osteoporosis

Strategies of Macrophages to Maintain Bone Homeostasis and Promote Bone Repair: A Narrative Review

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