Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Menale, Ciro, Tabacco, Gaia, Naciu, Anda Mihaela, Schiavone, Maria Lucia, Cannata, Francesca, Morenghi, Emanuela, Sobacchi, Cristina, Palermo, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784734168683380736
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
work_keys_str_mv AT menaleciro dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT tabaccogaia dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT naciuandamihaela dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT schiavonemarialucia dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT cannatafrancesca dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT morenghiemanuela dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT sobacchicristina dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen
AT palermoandrea dipeptidylpeptidase3activityasapromisingbiomarkerofbonefragilityinpostmenopausalwomen