{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:24:49Z","timestamp":1790630689950,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T00:00:00Z","timestamp":1655596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1\u2013Nrf2 antioxidant pathway. The absence of Dpp3 in the Dpp3 knockout mouse model causes increased osteoclast activity, altered osteogenic function, sustained oxidative stress in the bone tissue, and bone loss. We aimed to assess the association of Dpp3 activity with bone fragility in postmenopausal osteoporosis and the impact of denosumab on enzymatic activity. We conducted a two-phase study including 69 postmenopausal women with severe osteoporosis and 36 postmenopausal women without osteometabolic conditions, as controls (cross-sectional phase). Subjects with severe osteoporosis were assessed at baseline and 14 days after the first denosumab administration (prospective phase). The results showed significant reduction in serum Dpp3 activity (expressed as nmoles of formed product\/mg proteins\/min) in patients vs. controls (0.791 \u00b1 0.232 vs. 1.195 \u00b1 0.338; p &lt; 0.001), and significant association with bone mass at the femoral neck (r = 0.28, p = 0.02) in patients prior to treatment. We found a negative correlation between C-terminal telopeptide (CTX) or N-terminal pro-peptide of type 1 procollagen (P1NP) levels and Dpp3 activity (respectively, r = \u22120.29, p = 0.012; and r = \u22120.2572, p = 0.033). Dpp3 activity did not change after denosumab injection. Our findings support a critical role played by Dpp3 in bone homeostasis as a potential bone protective factor. Additional clinical studies in larger cohorts might explore the implementation of Dpp3 assessment as a biomarker of bone health status.<\/jats:p>","DOI":"10.3390\/molecules27123929","type":"journal-article","created":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T10:14:52Z","timestamp":1655633692000},"page":"3929","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5782-2089","authenticated-orcid":false,"given":"Ciro","family":"Menale","sequence":"first","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"},{"name":"Department of Clinical Medicine and Surgery, University of Naples \u201cFederico II\u201d, Via Pansini 5, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Tabacco","sequence":"additional","affiliation":[{"name":"Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4576-3381","authenticated-orcid":false,"given":"Anda Mihaela","family":"Naciu","sequence":"additional","affiliation":[{"name":"Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6728-3701","authenticated-orcid":false,"given":"Maria Lucia","family":"Schiavone","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-1950","authenticated-orcid":false,"given":"Francesca","family":"Cannata","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Morenghi","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sobacchi","sequence":"additional","affiliation":[{"name":"IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Italy"},{"name":"CNR-IRGB, Milan Unit, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-4926","authenticated-orcid":false,"given":"Andrea","family":"Palermo","sequence":"additional","affiliation":[{"name":"Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1111\/j.1742-4658.2011.08275.x","article-title":"Dipeptidyl Peptidase III: A Multifaceted Oligopeptide N-End Cutter","volume":"278","author":"Prajapati","year":"2011","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23787","DOI":"10.1038\/srep23787","article-title":"Substrate Complexes of Human Dipeptidyl Peptidase III Reveal the Mechanism of Enzyme Inhibition","volume":"6","author":"Kumar","year":"2016","journal-title":"Sci. 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