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Here, we identified that a selective PPAR \u03b3 modulator, Bavachinin (BVC), isolated from the seeds of <jats:italic>Psoralea Corylifolia<\/jats:italic> L., could potently regulate bone homeostasis. MC3T3\u2010E1 pre\u2010osteoblast cells and C3H10T1\/2 mesenchymal stem cells were assessed for osteogenic differentiation activities, and receptor activator of NF\u2010\u03baB ligand (RANKL)\u2010induced RAW 264.7 cells were assessed osteoclasts formation. Leptin receptor\u2010deficient mice and diet\u2010induced obesity mice were applied to evaluate the effect of BVC on bone homeostasis in vivo. Compared to full PPAR \u03b3 agonist rosiglitazone, BVC significantly increased the osteogenesis differentiation activities under normal and high glucose conditions in MC3T3\u2010E1 cells. Moreover, BVC could alleviate osteoclast differentiation in RANKL\u2010induced RAW 264.7 cells. In vivo, synthesized BVC prodrug (BN) has been applied to improve water solubility, increase the extent of oral absorption of BVC and prolong its residence time in blood circulation. BN could prevent weight gain, ameliorate lipid metabolism disorders, improve insulin sensitivity, and maintain bone mass and bone biomechanical properties. BVC, a unique PPAR \u03b3 selective modulator, could maintain bone homeostasis, and its prodrug (BN) exhibits insulin sensitizer activity while circumventing the side effects of the TZDs, including bone loss and undesirable weight gain.<\/jats:p>","DOI":"10.1002\/ptr.7912","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T03:05:31Z","timestamp":1686625531000},"page":"4457-4472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Bavachinin selectively modulates <scp>PPAR<\/scp> \u03b3 and maintains bone homeostasis in <scp>Type 2 Diabetes<\/scp>"],"prefix":"10.1002","volume":"37","author":[{"given":"Jingwen","family":"Liu","sequence":"first","affiliation":[{"name":"Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoye","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ren","sequence":"additional","affiliation":[{"name":"Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4073-4773","authenticated-orcid":false,"given":"Fujiang","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.8.5128"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202009200"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01225.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13887"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-021-01385-5"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-012-2240-z"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09291"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-014-1913-x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1010949"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acc.2021.06.001"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2009.214"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2008-0127"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2021.01.023"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-3912-9"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200401138"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.10.023"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(96)00258-X"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-007-0477-y"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28449E"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2018.05.004"},{"key":"e_1_2_10_24_1","unstructured":"International Diabetes Federation. 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