Identification of novel collagen breakdown products by human osteoclasts in vitro and in vivo
Rattachement africain : gb, jo, ca. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Bone resorption involves dissolution of minerals and enzymatic degradation of bone matrix. The primary enzyme is cathepsin K but other proteases including matrix metalloproteinases are involved. Some cathepsin K cleavage products have been partially identified, including cross-linked telopeptides of type I collagen. Here, we aimed to characterize the entire complement of bone breakdown products resulting from osteoclast action under controlled conditions in vitro. We analyzed extracellular media from human osteoclasts cultured on dentin substrates, using untargeted liquid chromatography mass spectrometry. We discovered 22 breakdown products resulting from osteoclastic action. These products were peptide fragment sequences that mapped to various collagen proteins present in bone and dentin. Nine peptide fragments mapped exclusively to collagen I alpha-1 chain (COL1A1), the most abundant protein in bone. We subsequently detected 21 of the fragment products, initially observed in vitro, in human serum and/or urine. Consistent positive correlations were observed between the COL1A1-specific peptide fragments and established bone biochemical markers in serum and urine. Ten urine fragments and two serum fragments markedly increased (p < .05) following total hip arthroplasty, capturing the transient local peri-prosthetic osteolysis observed in these patients (serum, n = 86 patients; urine, n = 83 patients). Among these candidate osteolytic markers, four (two COL1A1-specific products) showed decreases from baseline (p < .05) in patients on denosumab (n = 10 patients). Additionally, two fragment peptides were higher (p < .05, fold change >2) in urine from patients with bone metastasis (24 out of 112) among a lung cancer cohort. The range of collagen peptide fragments we discovered as a direct result of osteoclast activity indicates a complexity of bone resorption pathways not previously known, extending beyond the known proteolytic cleavage events in bone collagen proteins. Monitoring biofluid concentrations of these novel bone markers has the potential to capture multiple pathways of bone resorption activity beyond the existing assays based on cathepsin K.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Identification of novel collagen breakdown products by human osteoclasts in vitro and in vivo
- Date Crossref
- 11/10/2025
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Liverpool Department of Musculoskeletal and Ageing Science pays non établi dans la noticeUniversité ou école supérieure
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Mutah University pays non établi dans la noticeUniversité ou école supérieure
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Royal Liverpool University Hospital Department of Clinical Biochemistry and Metabolic Medicine pays non établi dans la noticeÉtablissement de santé
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Clatterbridge Cancer Centre NHS Foundation Trust pays non établi dans la noticeÉtablissement de santé
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Ottawa Hospital Department of Surgery pays non établi dans la noticeÉtablissement de santé
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University of Sheffield Department of Oncology and Metabolism pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Allied Medical Sciences Department of Medical Laboratory Sciences pays non établi dans la noticeUniversité ou école supérieure
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Department of Palliative Medicine pays non établi dans la noticeInstitution
Department of Musculoskeletal and Ageing Science — University of Liverpool, Mutah University et Department of Clinical Biochemistry and Metabolic Medicine — Royal Liverpool University Hospital, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.