Effects of sleeve gastrectomy on bone mass, microstructure of femurs and bone metabolism associated serum factors in obese rats

Abstract Background Sleeve gastrectomy (SG) is a profoundly effective operation for severe obese patients, but is closely associated with bone mass loss. Previous studies have reported changes of various serum factors which may be associated with bone mass loss after SG. However, those results are contradictory. In this study, we assessed the effects of SG on bone mass, microstructure of femurs, and changes in bone turnover markers (BTMs), serum adipokines, inflammatory factors and gastrointestinal hormones after SG in high-fat diet (HFD) induced obese rats. Methods Eight-week-old male Sprague–Dawley (SD) rats were fed with HFD to induce obesity. Then, SG and sham surgery were performed in anesthetized obese rats. SD rats in control group were fed with standard chow. Microstructure of femurs was scanned and analyzed by micro-computed tomography in control group, HFD sham group and HFD SG group. Serum inflammatory factors, adipokines markers, gastrointestinal hormones and BTMs were also measured. Results Bone mineral density (BMD) of trabecular bone in both HFD sham group and HFD SG group were remarkably decreased compared with control group. All serum BTMs were significantly higher in HFD SG group than HFD sham group. In the meantime, serum levels of several important inflammatory factors, gastrointestinal hormones and adipokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein-1(MCP-1), ghrelin, insulin and leptin in HFD SG group were remarkably reduced compared with HFD sham group, whereas glucagon-like peptide-1 (GLP-1), adiponectin, fibroblast growth factor (FGF)-19 and FGF-21 were dramatically increased after SG. Protein tyrosine phosphatase 1B (PTP1B) was significantly increased in the HFD sham group than control group. Spearman’s correlation analysis indicated that serum osteocalcin (OC) and 25-hydroxy vitamin D3 (25(OH)D3) were positively correlated with BMD of trabecular bone, whereas serum PTP1B and TNF-α were negatively related to BMD of trabecular bone. Conclusions SG aggravates bone mass loss and activates bone remodeling in obese rats. Levels of BTMs, adipokines, inflammatory factors, and gastrointestinal hormones could be affected by SG in obese rats. Serum PTP1B level might be associated with abnormal bone mass in obese rats.

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Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats

Experimental Biology and Medicine ◽

10.1177/15353702211011052 ◽

2021 ◽

pp. 153537022110110

Author(s):

Yu-Ting Cheng ◽

Jian Liao ◽

Qian Zhou ◽

Hua Huo ◽

Lucas Zellmer ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Mass ◽

Mass Loss ◽

Ovariectomized Rats ◽

Therapeutic Effects ◽

Bone Mass Loss ◽

Cellular Effects ◽

Protein Levels ◽

Adverse Factor ◽

Osteoclast Apoptosis

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.

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Ipriflavone effect on prevention and treatment of postmenopausal bone mass loss. Relation to estrogen replacement therapy

Osteoporosis International ◽

10.1007/bf02500477 ◽

1996 ◽

Vol 6 (S1) ◽

pp. 235-235

Author(s):

M. R. Ulla ◽

R. Díaz

Keyword(s):

Bone Mass ◽

Mass Loss ◽

Replacement Therapy ◽

Estrogen Replacement Therapy ◽

Estrogen Replacement ◽

Bone Mass Loss ◽

Prevention And Treatment

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HORMONE REPLACEMENT THERAPY AND CALCITONIN IN WOMEN WITH BONE MASS LOSS

Bone ◽

10.1016/j.bone.2010.01.035 ◽

2010 ◽

Vol 46 ◽

pp. S20

Author(s):

Antonio Bazarra-Fernandez

Keyword(s):

Hormone Replacement Therapy ◽

Bone Mass ◽

Mass Loss ◽

Replacement Therapy ◽

Hormone Replacement ◽

Bone Mass Loss

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Bromodomain Protein BRD4 Accelerates Glucocorticoid Dysregulation of Bone Mass and Marrow Adiposis by Modulating H3K9 and Foxp1

Cells ◽

10.3390/cells9061500 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1500

Author(s):

Feng-Sheng Wang ◽

Yu-Shan Chen ◽

Jih-Yang Ko ◽

Chung-Wen Kuo ◽

Huei-Jing Ke ◽

...

Keyword(s):

Bone Mass ◽

Mass Loss ◽

Osteogenic Differentiation ◽

Progenitor Cells ◽

Mesenchymal Progenitor Cells ◽

Marrow Fat ◽

Bone Mass Loss ◽

Brd4 Inhibition ◽

The Cost

Glucocorticoid provokes bone mass loss and fatty marrow, accelerating osteoporosis development. Bromodomain protein BRD4, an acetyl–histone-binding chromatin reader, regulates stem cell and tissue homeostasis. We uncovered that glucocorticoid inhibited acetyl Lys-9 at the histone 3 (H3K9ac)-binding Runx2 promoter and decreased osteogenic differentiation, whereas bromodomain protein 4 (BRD4) and adipocyte formation were upregulated in bone-marrow mesenchymal progenitor cells. BRD4 knockdown improved H3K9ac occupation at the Runx2 promoter and osteogenesis, but attenuated glucocorticoid-mediated adipocyte formation together with the unaffected H3K9ac-binding PPARγ2 promoter. BRD4 regulated epigenome related to fatty acid metabolism and the forkhead box P1 (Foxp1) pathway, which occupied the PPARγ2 promoter to modulate glucocorticoid-induced adipocytic activity. In vivo, BRD4 inhibitor JQ-1 treatment mitigated methylprednisolone-induced suppression of bone mass, trabecular microstructure, mineral acquisition, and osteogenic differentiation. Foxp1 signaling, marrow fat, and adipocyte formation in glucocorticoid-treated skeleton were reversed upon JQ-1 treatment. Taken together, glucocorticoid-induced H3K9 hypoacetylation augmented BRD4 action to Foxp1, which steered mesenchymal progenitor cells toward adipocytes at the cost of osteogenic differentiation in osteoporotic skeletons. BRD4 inhibition slowed bone mass loss and marrow adiposity. Collective investigations convey a new epigenetic insight into acetyl histone reader BRD4 control of osteogenesis and adipogenesis in skeleton, and highlight the remedial effects of the BRD4 inhibitor on glucocorticoid-induced osteoporosis.

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