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Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women
The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1–Nrf2 antioxidant pathway. The absence of Dpp3 in the Dpp3 knockout mouse model causes increased osteoclast activity, altered osteogen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227407/ https://www.ncbi.nlm.nih.gov/pubmed/35745051 http://dx.doi.org/10.3390/molecules27123929 |
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author | Menale, Ciro Tabacco, Gaia Naciu, Anda Mihaela Schiavone, Maria Lucia Cannata, Francesca Morenghi, Emanuela Sobacchi, Cristina Palermo, Andrea |
author_facet | Menale, Ciro Tabacco, Gaia Naciu, Anda Mihaela Schiavone, Maria Lucia Cannata, Francesca Morenghi, Emanuela Sobacchi, Cristina Palermo, Andrea |
author_sort | Menale, Ciro |
collection | PubMed |
description | The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1–Nrf2 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 ± 0.232 vs. 1.195 ± 0.338; p < 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 = −0.29, p = 0.012; and r = −0.2572, 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. |
format | Online Article Text |
id | pubmed-9227407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92274072022-06-25 Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women Menale, Ciro Tabacco, Gaia Naciu, Anda Mihaela Schiavone, Maria Lucia Cannata, Francesca Morenghi, Emanuela Sobacchi, Cristina Palermo, Andrea Molecules Article The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1–Nrf2 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 ± 0.232 vs. 1.195 ± 0.338; p < 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 = −0.29, p = 0.012; and r = −0.2572, 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. MDPI 2022-06-19 /pmc/articles/PMC9227407/ /pubmed/35745051 http://dx.doi.org/10.3390/molecules27123929 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Menale, Ciro Tabacco, Gaia Naciu, Anda Mihaela Schiavone, Maria Lucia Cannata, Francesca Morenghi, Emanuela Sobacchi, Cristina Palermo, Andrea Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women |
title | Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women |
title_full | Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women |
title_fullStr | Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women |
title_full_unstemmed | Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women |
title_short | Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women |
title_sort | dipeptidyl peptidase 3 activity as a promising biomarker of bone fragility in postmenopausal women |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227407/ https://www.ncbi.nlm.nih.gov/pubmed/35745051 http://dx.doi.org/10.3390/molecules27123929 |
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