{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T09:45:05Z","timestamp":1794649505425,"version":"4.9.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Liverpool, Royal Liverpool University Hospital and Agilent Technologies UK Ltd"},{"name":"Sireau Career Development Fellowship awarded to BPN by the Alkaptonuria Society","award":["#1101052"],"award-info":[{"award-number":["#1101052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2009&amp;lt;\u2009.05) following total hip arthroplasty, capturing the transient local peri-prosthetic osteolysis observed in these patients (serum, n\u2009=\u200986 patients; urine, n\u2009=\u200983 patients). Among these candidate osteolytic markers, four (two COL1A1-specific products) showed decreases from baseline (p\u2009&amp;lt;\u2009.05) in patients on denosumab (n\u2009=\u200910 patients). Additionally, two fragment peptides were higher (p\u2009&amp;lt;\u2009.05, fold change &amp;gt;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.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf160","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T11:53:41Z","timestamp":1760183621000},"source":"Crossref","is-referenced-by-count":3,"title":["Identification of novel collagen breakdown products by human osteoclasts in vitro and in vivo"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9293-4852","authenticated-orcid":false,"given":"Brendan P","family":"Norman","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , West Derby Street, Liverpool , L7 8TX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane P","family":"Dillon","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , West Derby Street, Liverpool , L7 8TX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahem M","family":"Alkharabsheh","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Mutah University, Alkarak 61710 ,","place":["Jordan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Congues","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , West Derby Street, Liverpool , L7 8TX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , West Derby Street, Liverpool , L7 8TX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5501-4475","authenticated-orcid":false,"given":"Andrew S","family":"Davison","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Royal Liverpool University Hospitals Trust , Mount Vernon Street, Liverpool , L7 8YE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elinor","family":"Chapman","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool , Crown Street, Liverpool , L69 7BE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Baker","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool , Crown Street, Liverpool , L69 7BE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9amus","family":"Coyle","sequence":"additional","affiliation":[{"name":"Liverpool Head and Neck Cancer Centre, University of Liverpool ,","place":["West Derby Street, Liverpool, L7 8TX, United Kingdom"]},{"name":"Department of Palliative Medicine, Clatterbridge Cancer Centre , Pembroke Place, Liverpool , L7 8YA,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Probert","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool , Crown Street, Liverpool , L69 7BE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E","family":"Beaul\u00e9","sequence":"additional","affiliation":[{"name":"Department of Surgery, The Ottawa Hospital , Smyth Road, Ottawa, Ontario K1H 8L6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshminarayan R","family":"Ranganath","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , West Derby Street, Liverpool , L7 8TX,","place":["United Kingdom"]},{"name":"Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Royal Liverpool University Hospitals Trust , Mount Vernon Street, Liverpool , L7 8YE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield , Beech Hill Road, Sheffield , S10 2RX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool , West Derby Street, Liverpool , L7 8TX,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,11]]},"reference":[{"issue":"4920","key":"2025111608424226200_ref1","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1126\/science.2528207","article-title":"Osteoclastic bone resorption by a polarized vacuolar proton 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