{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:11:20Z","timestamp":1772989880819,"version":"3.50.1"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Increased fracture risk in prediabetes and diabetes mellitus partly arises from bone collagen damage and enhanced bone resorption. Certain antidiabetic agents\u2014particularly thiazolidinediones\u2014paradoxically aggravate bone loss and fractures, especially in postmenopausal women with osteoporosis. However, dipeptidyl peptidase\u20104 (DPP\u20104) inhibitors (e.g., vildagliptin and omarigliptin) might help prevent diabetic osteopathy, although variable outcomes have been observed due to unknown mechanisms. Herein, we used high\u2010fat diet\u2010fed rats to demonstrate that oral administration of vildagliptin for 4\u2009weeks not only alleviated insulin resistance but also improved tibial bone microstructure, as determined by bone histomorphometry. Further in\u00a0vitro investigations in primary osteoblasts showed that both vildagliptin and omarigliptin similarly increased osteoblast viability, rather than upregulating the expression of osteoblast\u2010specific genes (e.g., Runx2 and alkaline phosphatase). We also used primary multinucleated osteoclasts to elucidate how the two DPP\u20104 inhibitors modulated osteoclast functions. Interestingly, only omarigliptin, but not vildagliptin, reduced the number of TRAP\u2010positive cells and the mRNA expression of osteoclast\u2010specific genes (e.g., RANK and cathepsin K).\n                    <jats:italic>In silico<\/jats:italic>\n                    molecular dynamics revealed that omarigliptin and vildagliptin interacted differently with the DPP\u20104 homodimer. Transient binding to one chain and tight binding to the other chain of the DPP\u20104 homodimer by omarigliptin may be associated with its higher potency in inhibiting bone resorption. In conclusion, DPP\u20104 inhibitors could improve bone microstructure, in part by increasing osteoblast viability and inhibiting osteoclast\u2010mediated bone resorption. Thus, omarigliptin may offer greater benefits to diabetic patients with osteoporosis, as it also helps suppress osteoclastogenesis and bone resorption.\n                  <\/jats:p>","DOI":"10.1002\/cph4.70103","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:58:07Z","timestamp":1769061487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vildagliptin and Omarigliptin Differentially Bind to DPP\u20104 Homodimers and Modulate Osteoclast\u2010Mediated Bone Resorption"],"prefix":"10.1002","volume":"16","author":[{"given":"Ratchaneevan","family":"Aeimlapa","sequence":"first","affiliation":[{"name":"Center of Calcium and Bone Research (COCAB), Faculty of Science Mahidol University  Bangkok Thailand"},{"name":"Department of Physiology, Faculty of Science Mahidol University  Bangkok 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