{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:06:30Z","timestamp":1789387590073,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32101883"],"award-info":[{"award-number":["32101883"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ift.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Food Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Collagen peptides (CPs) have emerged as a promising food\u2010derived strategy to enhance calcium utilization and osteogenesis, notably through specific calcium binding via chelation. However, conventional separation methods often fail to efficiently isolate peptides with high calcium\u2010binding affinity, resulting in products with limited osteogenic activity. In this study, hydroxyapatite affinity chromatography (HAC) was employed, leveraging its dual ion\u2010exchange and affinity properties, to enrich bovine\u2010bone\u2010derived CPs with high calcium\u2010binding capacity. The purified fraction (F2) exhibited a significantly higher calcium\u2010binding capacity (42.44\u00a0\u00b5g\/mg) than unpurified CPs and was enriched in low\u2010molecular\u2010weight (LMW) peptides (1\u20133\u00a0kDa) rich in acidic amino acids (Asp and Glu). After calcium chelation, structural analysis (e.g., FTIR, SEM, and AFM) confirmed its effective calcium\u2010binding capacity and conformational changes. In addition, in vitro assays demonstrated that F2 markedly promoted MC3T3\u2010E1 osteoblast proliferation, differentiation, and mineralization compared with CPs, presenting enhanced osteogenic bioactivity. Molecular docking further indicated that key peptides may bind to the osteogenic receptors BMPR1 and TGFBR1, raising the possibility that the TGF\u2010\u03b2\/BMP signaling pathways could be involved. Collectively, our findings indicate that HAC is an effective strategy for enriching osteogenic CPs with high calcium\u2010binding and osteogenic activity, offering a scalable strategy for producing potent peptides applicable to bone health management and therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Practical Applications<\/jats:title>\n                    <jats:p>This study provides a scalable method for extracting highly active calcium\u2010binding peptides from collagen peptides using a hydroxyapatite column. These purified peptides can be developed into functional food ingredients or dietary supplements to support bone health. By improving calcium delivery efficiency and direct osteogenic activity, this approach offers a science\u2010based strategy for next\u2010generation bone health products.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1750-3841.71272","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T03:40:38Z","timestamp":1783309238000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Isolation of Novel Calcium\u2010Binding Peptides via Hydroxyapatite Affinity and Their Promotion Effect on Osteogenesis in MC3T3\u2010E1 Cells"],"prefix":"10.1111","volume":"91","author":[{"given":"Changyan","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Agro\u2010Products Processing Institute of Food Science and Technology Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro\u2010Products Processing Institute of Food Science and Technology Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro\u2010Products Processing Institute of Food Science and Technology Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishmael Festus","family":"Jaja","sequence":"additional","affiliation":[{"name":"Department of Livestock and Pasture Science University of Fort Hare  Alice South Africa"},{"name":"Department of Agriculture and Animal Health Florida Campus University of South Africa  Pretoria South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro\u2010Products Processing Institute of Food Science and Technology Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5268-311X","authenticated-orcid":false,"given":"Xiaojie","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro\u2010Products Processing Institute of Food Science and Technology Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1411-4047","authenticated-orcid":false,"given":"Chunhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agro\u2010Products Processing Institute of Food Science and Technology Ministry of Agriculture and Rural Affairs, Chinese Academy of Agricultural Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/separations11080233"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2018.01.038"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2019.110990"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2023.464530"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9FO01335K"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2015.10.017"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fochx.2024.101706"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121500"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022202"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1337407"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2025.146183"},{"key":"e_1_2_9_13_1","first-page":"3","article-title":"Purification and Characterization of a Novel Calcium\u2010Binding Heptapeptide From the Hydrolysate of Tilapia Bone With Its Osteogenic Activity","volume":"11","author":"He J. 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