{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:24:17Z","timestamp":1787855057790,"version":"build-2784847793"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chondrocalcin (CCN), the C\u2010terminal propeptide of type II procollagen and a key regulatory peptide in collagen assembly, is abundantly expressed in cartilage and implicated in bone\u2010cartilage interface disorders. We engineered a\n                    <jats:italic>Pichia pastoris<\/jats:italic>\n                    strain via genetic modification to produce recombinant chondrocalcin (rCCN), which was isolated, purified, and characterized. Functional assays revealed that rCCN promotes human bone marrow mesenchymal stem cell (hBMSC) differentiation into chondrocytes. Mechanistically, rCCN at 0.3\u2009mg\/mL promoted hBMSC chondrogenesis via SOX9\/COLII\/aggrecan upregulation (2.84\u2010, 7.94\u2010, 9.13\u2010fold) while suppressing fibrotic COL I. In rheumatoid arthritis synoviocytes (HFLS\u2010RA), rCCN reprogrammed the inflammatory microenvironment via the upregulation of COLII\/IL\u20104\/TGF\u2010\u03b21 upregulating (0.69\u2010, 4.01\u2010, 1.18\u2010fold), and the downregulating TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106. These findings highlight rCCN's dual therapeutic potential as a biomaterial for cartilage repair and inflammatory modulation.\n                  <\/jats:p>","DOI":"10.1002\/bit.70256","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:08:28Z","timestamp":1781172508000},"page":"2275-2288","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineered Chondrocalcin From\n                    <i>Pichia pastoris<\/i>\n                    : A Dual\u2010Functional Biomaterial for Cartilage Regeneration and Rheumatoid Arthritis Modulation"],"prefix":"10.1002","volume":"123","author":[{"given":"Wensha","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Chemical Engineering, Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education Northwest University Xi'an China"},{"name":"School of Chemical Engineering, Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&amp;D Center of Biomaterials and Fermentation Engineering Northwest University Xi'an China"},{"name":"Biotech. &amp; Biomed. Research Institute Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5584-1972","authenticated-orcid":false,"given":"Zilong","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education Northwest University Xi'an China"},{"name":"School of Chemical Engineering, Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&amp;D Center of Biomaterials and Fermentation Engineering Northwest University Xi'an China"},{"name":"Biotech. &amp; Biomed. Research Institute Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weigang","family":"Yuwen","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&amp;D Center of Biomaterials and Fermentation Engineering Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education Northwest University Xi'an China"},{"name":"School of Chemical Engineering, Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&amp;D Center of Biomaterials and Fermentation Engineering Northwest University Xi'an China"},{"name":"Biotech. &amp; Biomed. Research Institute Northwest University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education Northwest University Xi'an China"},{"name":"School of Chemical Engineering, Shaanxi Key Laboratory of Biomaterials and Synthetic Biology, Shaanxi R&amp;D Center of Biomaterials and Fermentation Engineering Northwest University Xi'an China"},{"name":"Biotech. &amp; Biomed. 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