PPAR激动剂治疗骨质疏松症的研究进展

摘要/Abstract

摘要： 过氧化物酶增殖激活受体（PPAR）是核激素受体，包括3种亚型：PPARα、PPARβ/δ、PPARγ。PPARα与脂质分解代谢、炎症有关，PPARβ/δ与哺乳动物皮肤、肝脏和骨骼再生有关，PPARγ与脂肪形成、葡萄糖稳态有关。本文主要就PPAR激动剂在治疗骨质疏松症的研究现状作一综述。

关键词:

PPAR, PPAR激动剂；骨质疏松症

Abstract: Peroxisome proliferator-activated receptors（PPARs） are ligand-stimulating receptors in the nuclear receptor family, including three isotypes：PPARα、PPARβ／δ and PPARγ. PPARα has been implicated as a major regulator of lipid metabolism and inflammation, PPARβ／δ appears to be associated with mammalian skin, liver and bone regeneration, PPARγ has emerged as a key regulator of fat formation and glucose homeostasis. This review summarizes our current knowledge of PPARs agonists in processes associated with osteoporosis.

中图分类号:

R683.4

钱钧孙瑶. PPAR激动剂治疗骨质疏松症的研究进展[J]. 口腔生物医学, 2021, 12(1): 58-61.

Jun QIAN. PPARs agonists for the treatment of osteoporosis[J]. Oral Biomedicine, 2021, 12(1): 58-61.

参考文献 94

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[35]	Lefere S, Puengel T, Hundertmark J, et al.Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages[J].J Hepatol, 2020, 73(4):757-770
[36]	Tan C K, Zhuang Y, Wahli W.Synthetic and natural Peroxisome Proliferator-Activated Receptor (PPAR) agonists as candidates for the therapy of the metabolic syndrome[J].Expert Opin Ther Targets, 2017, 21(3):333-348
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[38]	Chan B Y, Gartland A, Wilson P J, et al.PPAR agonists modulate human osteoclast formation and activity in vitro[J].Bone, 2007, 40(1):149-159
[39]	Matin A, Doddareddy M R, Gavande N, et al.The discovery of novel isoflavone pan peroxisome proliferator-activated receptor agonists[J].Bioorg Med Chem, 2013, 21(3):766-778
[40]	Feng L, Luo H, Xu Z, et al.Bavachinin,as a novel natural pan-PPAR agonist,exhibits unique synergistic effects with synthetic PPAR-gamma and PPAR-alpha agonists on carbohydrate and lipid metabolism in dbdb and diet-induced obese mice[J].Diabetologia, 2016, 59(6):1276-1286
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[42]	Kasonga A, Kruger M C, Coetzee M.Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes[J]. Int J Mol Sci, 2019, 20(7).
[43]	Djouad F, Ipseiz N, Luz-Crawford P, et al.PPARbetadelta: A master regulator of mesenchymal stem cell functions[J].Biochimie, 2017, 136:55-58
[44]	Magadum A, Engel F B.PPARbeta/delta: Linking Metabolism to Regeneration[J]. Int J Mol Sci, 2018, 19(7).
[45]	Wan Y, Chong L W, Evans R M.PPAR-gamma regulates osteoclastogenesis in mice[J].Nat Med, 2007, 13(12):1496-1503
[46]	Qiao W, Wang C, Huang W, et al.Peroxisome proliferator-activated receptor gamma plays dual roles on experimental periodontitis in rats[J].J Clin Periodontol, 2018, 45(5):514-523
[47]	Di Paola R, Briguglio F, Paterniti I, et al.Emerging role of PPAR-betadelta in inflammatory process associated to experimental periodontitis[J].Mediators Inflamm, 2011, 2011:787159-
[48]	[参考文献]
[49]	Mirza A Z, Althagafi I I, Shamshad H.Role of PPAR receptor in different diseases and their ligands: Physiological importance and clinical implications[J].Eur J Med Chem, 2019, 166:502-513
[50]	Capelli D, Cerchia C, Montanari R, et al.Structural basis for PPAR partial or full activation revealed by a novel ligand binding mode[J].Sci Rep, 2016, 6:34792-
[51]	Dubois V, Eeckhoute J, Lefebvre P, et al.Distinct but complementary contributions of PPAR isotypes to energy homeostasis[J].J Clin Invest, 2017, 127(4):1202-1214
[52]	Botta M, Audano M, Sahebkar A, et al.PPAR Agonists and Metabolic Syndrome: An Established Role?[J]. Int J Mol Sci, 2018, 19(4).
[53]	Papatheodorou K, Banach M, Bekiari E, et al.Complications of Diabetes 2017[J].J Diabetes Res, 2018, 2018:3086167-
[54]	Ensrud K E, Crandall C J.Osteoporosis[J].Ann Intern Med, 2017, 167(3):C17-C32
[55]	Kersten S, Desvergne B, Wahli W.Roles of PPARs in health and disease[J].Nature, 2000, 405(6785):421-424
[56]	Lee H Y, Gao X, Barrasa M I, et al.PPAR-alpha and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal[J].Nature, 2015, 522(7557):474-477
[57]	Bougarne N, Weyers B, Desmet S J, et al.Molecular Actions of PPARalpha in Lipid Metabolism and Inflammation[J].Endocr Rev, 2018, 39(5):760-802
[58]	Huang M S, Lu J, Ivanov Y, et al.Hyperlipidemia impairs osteoanabolic effects of PTH[J].J Bone Miner Res, 2008, 23(10):1672-1679
[59]	Kim Y H, Jang W G, Oh S H, et al.Fenofibrate induces PPARalpha and BMP2 expression to stimulate osteoblast differentiation[J].Biochem Biophys Res Commun, 2019, 520(2):459-465
[60]	Stunes A K, Westbroek I, Gustafsson B I, et al.The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass,while the PPAR gamma agonist pioglitazone exaggerates bone loss,in ovariectomized rats[J].BMC Endocr Disord, 2011, 11:11-
[61]	Mosti M P, Ericsson M, Erben R G, et al.The PPARalpha Agonist Fenofibrate Improves the Musculoskeletal Effects of Exercise in Ovariectomized Rats[J].Endocrinology, 2016, 157(10):3924-3934
[62]	Pang M, de la Monte S M, Longato L, et al.PPARdelta agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair[J].J Hepatol, 2009, 50(6):1192-1201
[63]	Neels J G, Grimaldi P A.Physiological functions of peroxisome proliferator-activated receptor beta[J].Physiol Rev, 2014, 94(3):795-858
[64]	Schug T T, Berry D C, Shaw N S, et al.Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors[J].Cell, 2007, 129(4):723-733
[65]	Magadum A, Ding Y, He L, et al.Live cell screening platform identifies PPARdelta as a regulator of cardiomyocyte proliferation and cardiac repair[J].Cell Res, 2017, 27(8):1002-1019
[66]	Maltarollo V G, Kronenberger T, Windshugel B, et al.Advances and Challenges in Drug Design of PPARdelta Ligands[J].Curr Drug Targets, 2018, 19(2):144-154
[67]	Scholtysek C, Katzenbeisser J, Fu H, et al.PPARbetadelta governs Wnt signaling and bone turnover[J].Nat Med, 2013, 19(5):608-613
[68]	Mosti M P, Stunes A K, Ericsson M, et al.Effects of the peroxisome proliferator-activated receptor (PPAR)-delta agonist GW501516 on bone and muscle in ovariectomized rats[J].Endocrinology, 2014, 155(6):2178-2189
[69]	Qian G, Fan W, Ahlemeyer B, et al.Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors[J].PLoS One, 2015, 10(12):e143439-
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[72]	Brun J, Berthou F, Trajkovski M, et al.Bone Regulates Browning and Energy Metabolism Through Mature OsteoblastOsteocyte PPARgamma Expression[J].Diabetes, 2017, 66(10):2541-2554
[73]	Lu W, Wang W, Wang S, et al.Rosiglitazone Promotes Bone Marrow Adipogenesis to Impair Myelopoiesis under Stress[J].PLoS One, 2016, 11(2):e149543-
[74]	Marciano D P, Kuruvilla D S, Boregowda S V, et al.Pharmacological repression of PPARgamma promotes osteogenesis[J].Nat Commun, 2015, 6:7443-
[75]	Briguglio E, Di Paola R, Paterniti I, et al.WY-14643,a Potent Peroxisome Proliferator Activator Receptor-alpha PPAR-alpha Agonist Ameliorates the Inflammatory Process Associated to Experimental Periodontitis[J].PPAR Res, 2010, 2010:193019-
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[77]	Jain M R, Giri S R, Bhoi B, et al.Dual PPARalphagamma agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models[J].Liver Int, 2018, 38(6):1084-1094
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[81]	Qi Z G, Zhao X, Zhong W, et al.Osthole improves glucose and lipid metabolism via modulation of PPARalphagamma-mediated target gene expression in liver,adipose tissue,and skeletal muscle in fatty liver rats[J].Pharm Biol, 2016, 54(5):882-888
[82]	Lefere S, Puengel T, Hundertmark J, et al.Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages[J].J Hepatol, 2020, 73(4):757-770
[83]	Tan C K, Zhuang Y, Wahli W.Synthetic and natural Peroxisome Proliferator-Activated Receptor (PPAR) agonists as candidates for the therapy of the metabolic syndrome[J].Expert Opin Ther Targets, 2017, 21(3):333-348
[84]	Zhong X, Xiu L L, Wei G H, et al.Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation[J].Acta Pharmacol Sin, 2011, 32(5):591-600
[85]	Chan B Y, Gartland A, Wilson P J, et al.PPAR agonists modulate human osteoclast formation and activity in vitro[J].Bone, 2007, 40(1):149-159
[86]	Matin A, Doddareddy M R, Gavande N, et al.The discovery of novel isoflavone pan peroxisome proliferator-activated receptor agonists[J].Bioorg Med Chem, 2013, 21(3):766-778
[87]	Feng L, Luo H, Xu Z, et al.Bavachinin,as a novel natural pan-PPAR agonist,exhibits unique synergistic effects with synthetic PPAR-gamma and PPAR-alpha agonists on carbohydrate and lipid metabolism in dbdb and diet-induced obese mice[J].Diabetologia, 2016, 59(6):1276-1286
[88]	Zhang T, Han W, Zhao K, et al.Psoralen accelerates bone fracture healing by activating both osteoclasts and osteoblasts[J].FASEB J, 2019, 33(4):5399-5410
[89]	Kasonga A, Kruger M C, Coetzee M.Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes[J]. Int J Mol Sci, 2019, 20(7).
[90]	Djouad F, Ipseiz N, Luz-Crawford P, et al.PPARbetadelta: A master regulator of mesenchymal stem cell functions[J].Biochimie, 2017, 136:55-58
[91]	Magadum A, Engel F B.PPARbeta/delta: Linking Metabolism to Regeneration[J]. Int J Mol Sci, 2018, 19(7).
[92]	Wan Y, Chong L W, Evans R M.PPAR-gamma regulates osteoclastogenesis in mice[J].Nat Med, 2007, 13(12):1496-1503
[93]	Qiao W, Wang C, Huang W, et al.Peroxisome proliferator-activated receptor gamma plays dual roles on experimental periodontitis in rats[J].J Clin Periodontol, 2018, 45(5):514-523
[94]	Di Paola R, Briguglio F, Paterniti I, et al.Emerging role of PPAR-betadelta in inflammatory process associated to experimental periodontitis[J].Mediators Inflamm, 2011, 2011:787159-