PPARG in osteocytes is essential for sclerostin expression, bone mass, marrow adiposity and TZD-induced bone loss

Baroi, Sudipta; Czernik, Piotr J.; Chougule, Amit; Griffin, Patrick R.; Lecka‐Czernik, Beata

doi:10.1101/2020.09.13.295378

Cited by 2 publications

(2 citation statements)

References 56 publications

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“…Agonist of PPARγ a serial of small molecules, which has been used as e cacious drugs for the treatment of diabetes mellitus, such as rosiglitazone and pioglitazone (24). However, one of the most notorious adverse effect of these drug is osteoporosis (25,26). For this reason, PPARγ agonist usually prescribed for the treatment of diabetes mellitus combing with bisphosphate, such as alendronate (27).…”

Section: Discussionmentioning

confidence: 99%

Lysyl Oxidase Down-Regulates The Osteoblastic Potential of BMP9 Through Inhibiting HIF-1α/Wnt/β-Catenin Axis in Mesenchymal Stem Cells

Deng

Luo

Deng

et al. 2021

Preprint

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Background: Bone morphogenetic protein 9 (BMP9) is one of excellent osteogenic factors, but it can also initiate adipogenesis concomitantly. Thus, the osteogenic potential of BMP9 may be enhanced if the adipogenesis were reduced. It was reported that lysyl oxidase (Lox) may function as a critical switcher for adipogenesis. Up to date, the role of Lox in BMP9-induced osteoblastic differentiation remains unknown.Methods: The effect and possible mechanism of Lox on the osteogenic function of BMP9 were evaluated with RT-PCR, western blotting, immunofluorescent and histochemical staining. The same results were also confirmed with the in vivo BMP9-induced ectopic bone formation model.Results: The mRNA and protein of Lox are both detectable in progenitor cells, and it was increased by BMP9 in 3T3-L1 cells. BMP9-induced Runx2, OPN and mineralization were all enhanced by inhibiting or silencing Lox, but reduced by exogenous Lox. BMP9 increased the mRNA level of c-Myc, which was enhanced by inhibiting Lox, so did the protein level of β-catenin. Effects of Lox specific inhibitor on BMP9-induced Runx2, OPN and mineralization were reduced obviously by silencing β-catenin. HIF-1α was up-regulated by BMP9, which was enhanced by inhibiting or silencing Lox, but decreased by Lox over-expression. The effects of Lox specific inhibitor on increasing BMP9-induced osteogenic markers were reduced greatly by silencing HIF-1α. On the contrary, the inhibitory effect of Lox on BMP9-induced osteoblastic markers was almost abolished by HIF-1α over-expression. BMP9-induced bone formation was increased by silencing Lox or over-expressing HIF-1α. The effect of silencing Lox on potentiating BMP9-induced bone formation was attenuated by silencing HIF-1α. Lox specific inhibitor increased the level of β-catenin and decreased that of SOST, but these effects were almost reversed by silencing HIF-1α.Conclusions: Lox may reducing the osteoblastic-induction function of BMP9 through inhibiting Wnt/β-catenin signal via down-regulation of HIF-1α partly.

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Section: Discussionmentioning

confidence: 99%

Lysyl Oxidase Down-Regulates The Osteoblastic Potential of BMP9 Through Inhibiting HIF-1α/Wnt/β-Catenin Axis in Mesenchymal Stem Cells

Deng

Luo

Deng

et al. 2021

Preprint

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“…PPARγ activation induces differentiation along the adipocyte lineage and suppresses osteoblast differentiation [3, 4]. In osteocytes, PPARγ regulates the expression of sclerostin [5]. In osteoclasts, PPARγ is essential for differentiation via support of RANKL signaling [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

Freid

Hussein

Schlezinger

2021

Preprint

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Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We observed that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in female C57BL6/J mice. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with Vh or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed a low- or high-fat diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high-fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat diet and accompanied by a significant decrease in serum bone formation markers. Our novel observations will provide new information on basic bone biology, potential therapeutic targets and toxicological pathways.

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PPARG in osteocytes is essential for sclerostin expression, bone mass, marrow adiposity and TZD-induced bone loss

Cited by 2 publications

References 56 publications

Lysyl Oxidase Down-Regulates The Osteoblastic Potential of BMP9 Through Inhibiting HIF-1α/Wnt/β-Catenin Axis in Mesenchymal Stem Cells

Lysyl Oxidase Down-Regulates The Osteoblastic Potential of BMP9 Through Inhibiting HIF-1α/Wnt/β-Catenin Axis in Mesenchymal Stem Cells

Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice

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