TNF-α and IL10 gene polymorphisms in women with postmenopausal osteoporosis

Kotrych, Daniel; Dziedziejko, Violetta; Safranow, Krzysztof; Sroczyński, Tomasz; Staniszewska, Marzena; Juzyszyn, Zygmunt; Pawlik, Andrzej

doi:10.1016/j.ejogrb.2016.01.037

Cited by 26 publications

(26 citation statements)

References 28 publications

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“…These were interesting findings that strongly indicated that TNF‐α tended to activate osteoblastogenesis rather than osteoclasts in the present included populations. In fact, previous investigations demonstrated that the paradoxical role of TNF‐α on osteogenic differentiation was based on the concentration of TNF‐α, the cell type, and also the exposure time . However, we did not conduct a detailed assessment of these conditioning factors because these data could not be extracted from the original article in the present included study.…”

Section: Discussionmentioning

confidence: 94%

“…As for the underlying mechanisms, the classical view believes that TNF‐α is a powerful bone‐resorbing cytokine that stimulates osteoclast progenitor proliferation and differentiation . However, it was recently discovered that TNF‐α also activates osteoblastogenesis . Therefore, TNF‐α might have a double regulating function in bone homeostasis and factors that affect the expression of TNF‐α are very likely to be associated with the pathogenesis of osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

“…Nine studies evaluated the associations between TNF-α G308A polymorphism (GG vs GA+AA) and BMD, in which eight studies focused on LS-BMD [9][10][11][12]15,16,19,21 and six studies focused on FN-BMD [10][11][12][13]15,16 (Figure 3). According to the results, the mutant genotypes did not significantly affect the BMD as compared with GG genotype based on either LS-BMD data (P = 0.55, I 2 = 60%) or FN-BMD data (P = 0.37, I 2 = 91%).…”

Section: Gg Vs Ga+aamentioning

confidence: 99%

“…In contrast, several other studies indicated that TNF‐α G308A had no significant influence on BMD . Furthermore, studies regarding the associations between TNF‐α gene polymorphisms and risk of osteoporosis also exhibited inconsistent conclusions . Therefore, there is a high degree of uncertainty with respect to the exact impact of TNF‐α gene polymorphisms on BMD values and osteoporosis risk, the elucidation of which still requires a general summary in addition to clinical studies.…”

Section: Introductionmentioning

confidence: 99%

“…9,13 Furthermore, studies regarding the associations between TNF-α gene polymorphisms and risk of osteoporosis also exhibited inconsistent conclusions. 12,[14][15][16] Therefore, there is a high degree of uncertainty with respect to the exact impact of TNF-α gene polymorphisms on BMD values and osteoporosis risk, the elucidation of which still requires a general summary in addition to clinical studies. Nevertheless, no such systematic investigation has been performed so far as we know.…”

Section: Introductionmentioning

confidence: 99%

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The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

Wang

et al. 2019

Int J of Rheum Dis

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Objective Fracture is a common consequence of osteoporosis and is associated with high morbidity and mortality. Recently, increasing evidence has suggested that polymorphisms in tumor necrosis factor‐α (TNF‐α) gene were associated with osteoporosis risk and bone mineral density (BMD), but results remain conflicting. We herein performed a meta‐analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. Methods The PubMed, EMBASE, Cochrane Library, CNKI (China National Knowledge Infrastructure) and Wan Fang databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed and all available data were accumulated. The pooled odds ratios (ORs) or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the relationships. Results A total of 15 studies involving 5273 subjects were included in our meta‐analysis. The GG genotype of TNF‐α G308A was associated with an increased risk of osteoporosis under a mutant model (GG vs GA+AA: OR = 0.63, 95% CI: 0.51‐0.77, P < 0.0001, I2 = 31%). Additionally, we also observed a significant association between G308A polymorphism and BMD of lumbar spine (AA vs GG: P = 0.01, I2 = 53%). However, TNF‐α T1031C, C857T and C863A polymorphisms had no obvious impacts on osteoporosis risk. Conclusions The present meta‐analysis demonstrated that TNF‐α G308A polymorphism may act as a potential candidate biomarker for screening, diagnosis, and treatment of osteoporosis, which will help improve individualized therapy of osteoporosis patients in clinics.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Gg Vs Ga+aamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

Wang

et al. 2019

Int J of Rheum Dis

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Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Cline-Smith

Axelbaum

Shashkova

et al. 2020

Journal of Bone and Mineral Research

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The loss of estrogen (E2) initiates a rapid phase of bone loss leading to osteoporosis in one‐half of postmenopausal women, but the mechanism is not fully understood. Here, we show for the first time how loss of E2 activates low‐grade inflammation to promote the acute phase of bone catabolic activity in ovariectomized (OVX) mice. E2 regulates the abundance of dendritic cells (DCs) that express IL‐7 and IL‐15 by inducing the Fas ligand (FasL) and apoptosis of the DC. In the absence of E2, DCs become long‐lived, leading to increased IL‐7 and IL‐15. We find that IL‐7 and IL‐15 together, but not alone, induced antigen‐independent production of IL‐17A and TNFα in a subset of memory T cells (TMEM). OVX of mice with T‐cell–specific ablation of IL15RA showed no IL‐17A and TNFα expression, and no increase in bone resorption or bone loss, confirming the role of IL‐15 in activating the TMEM and the need for inflammation. Our results provide a new mechanism by which E2 regulates the immune system, and how menopause leads to osteoporosis. The low‐grade inflammation is likely to cause or contribute to other comorbidities observed postmenopause. © 2020 American Society for Bone and Mineral Research.

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Osteoporosis and osteoblasts cocultured with adipocytes inhibit osteoblast differentiation by downregulating histone acetylation

Abuna

Almeida

Souza

et al. 2020

Journal Cellular Physiology

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Osteoporosis is characterized by decreased bone mass and adipocyte accumulation within the bone marrow that inhibits osteoblast maturation, leading to a high risk of fractures. Thus, we hypothesized that osteoblasts, besides being negatively affected by interacting with adipocytes, reduce the differentiation of neighboring osteoblasts through the same mechanisms that affect osteoblasts under osteoporotic conditions. We investigated the effect of osteoporosis on osteoblast differentiation and the effect of the conditioned medium of osteoblasts cocultured with adipocytes on the differentiation of other osteoblasts. Osteoporosis was induced by orchiectomy in rats and bone marrow mesenchymal stromal cells (MSCs) were differentiated into osteoblasts. Also, the bone marrow and adipose tissue MSCs were obtained from healthy rats and differentiated into osteoblasts and adipocytes, respectively. Messenger RNA expression, in situ alkaline phosphatase activity, and mineralization confirmed the inhibitory effect of osteoporosis on osteoblast differentiation. This harmful effect was mimicked by the in vitro model using the conditioned medium and it was demonstrated that osteoblasts keep the memory of the negative impact of interacting with adipocytes, revealing an unknown mechanism relevant to the osteoporotic bone loss. Finally, we showed the involvement of acetyl‐histone 3 (AcH3) in bone homeostasis as its reduction induced by osteoporosis and conditioned medium impaired osteoblast differentiation. The AcH3 involvement was proved by treating osteoblasts with Trichostatin A that recovered the AcH3 expression and osteoblast differentiation capacity in both situations. Together, our findings indicated that AcH3 might be a target for future studies focused on epigenetic‐based therapies to treat bone diseases.

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TNF-α and IL10 gene polymorphisms in women with postmenopausal osteoporosis

Cited by 26 publications

References 28 publications

The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

The associations of TNF‐α gene polymorphisms with bone mineral density and risk of osteoporosis: A meta‐analysis

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Osteoporosis and osteoblasts cocultured with adipocytes inhibit osteoblast differentiation by downregulating histone acetylation

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