{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:22:24Z","timestamp":1787761344335,"version":"build-2784847793"},"reference-count":16,"publisher":"ASME International","issue":"10","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.asme.org\/publications-submissions\/publishing-information\/legal-policies"}],"funder":[{"DOI":"10.13039\/100000146","name":"Division of Chemical, Bioengineering, Environmental, and Transport Systems","doi-asserted-by":"publisher","award":["2112085"],"award-info":[{"award-number":["2112085"]}],"id":[{"id":"10.13039\/100000146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000147","name":"Division of Civil, Mechanical and Manufacturing Innovation","doi-asserted-by":"publisher","award":["1554708"],"award-info":[{"award-number":["1554708"]}],"id":[{"id":"10.13039\/100000147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000121","name":"Division of Mathematical Sciences","doi-asserted-by":"publisher","award":["1748883"],"award-info":[{"award-number":["1748883"]}],"id":[{"id":"10.13039\/100000121","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000121","name":"Division of Mathematical Sciences","doi-asserted-by":"publisher","award":["2325171"],"award-info":[{"award-number":["2325171"]}],"id":[{"id":"10.13039\/100000121","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR073964"],"award-info":[{"award-number":["R01AR073964"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR081489"],"award-info":[{"award-number":["R01AR081489"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asmedigitalcollection.asme.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cartilage deterioration is a hallmark of osteoarthritis, and there is substantial interest in developing strategies for cartilage repair. Cyclical mechanical stimulation has been known for decades to drive synthesis of cartilage matrix proteins. Matrix synthesis requires activation of central metabolism for producing precursors to nonessential amino acids required for protein translation. However, there are gaps in knowledge regarding how mechanical stimuli affect chondrocyte central metabolism. Here, we find that cyclical shear and compression drive differences in chondrocyte central metabolism in a sex-dependent manner. Based on established biochemistry, we developed and tested a stoichiometric model containing 139 metabolites and 172 reactions from central metabolism that includes production of key cartilage matrix proteins. We then used experimental metabolomics data from shear and compressive stimulation of osteoarthritic chondrocytes to constrain this model and ran multiple simulations examining the potential for producing matrix proteins and ATP. Our results show that both shear and compression can stimulate osteoarthritic chondrocyte metabolism in a manner consistent with production of cartilage matrix proteins, with notable differences between male and female chondrocytes. Additionally, and importantly, our simulation results suggest that nitrogen availability is a key limitation to chondrocyte synthesis of matrix proteins. These results are a starting point for using central metabolism of chondrocytes to optimize synthesis of matrix proteins for cartilage repair. For example, increasing glutamine levels in the presence of cyclical compression has potential to increase production of both types II and VI collagen. These strategies have potential for improving cartilage tissue engineering and repair.<\/jats:p>","DOI":"10.1115\/1.4072447","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T06:47:51Z","timestamp":1785912471000},"update-policy":"https:\/\/doi.org\/10.1115\/crossmarkpolicy-asme","source":"Crossref","is-referenced-by-count":0,"title":["Expanded Stoichiometric Model of Chondrocyte Metabolism: Response to Cyclical Shear and Compressive Loading"],"prefix":"10.1115","volume":"148","author":[{"given":"Aubrey H.","family":"Kimmel","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02w0trx84","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Mathematical Sciences, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne D.","family":"Arnold","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02w0trx84","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Microbiology and Cell Biology, Center for Biofilm Engineering, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-1345","authenticated-orcid":false,"given":"Ayten E.","family":"Erdogan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03g03ge92","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Chemical and Biological Engineering, Center for Biofilm Engineering, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronak","family":"Kommineni","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02w0trx84","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Mechanical and Industrial Engineering, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik P.","family":"Myers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02w0trx84","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Mechanical and Industrial Engineering, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-5277","authenticated-orcid":false,"given":"Breschine","family":"Cummins","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02w0trx84","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Mathematical Sciences, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross P.","family":"Carlson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03g03ge92","id-type":"ROR","asserted-by":"publisher"}],"name":"Montana State University Department of Chemical and Biological Engineering, Center for Biofilm Engineering, , Bozeman, MT 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-4109","authenticated-orcid":false,"suffix":"II","given":"Ronald K.","family":"June","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Industrial Engineering, Montana State University , P.O. Box 173800 , Bozeman, MT 59717-3800 ; , Bozeman, MT 59717 ; , Seattle, WA 98195"},{"name":"Department of Microbiology and Cell Biology, Center for Biofilm Engineering, Montana State University , P.O. Box 173800 , Bozeman, MT 59717-3800 ; , Bozeman, MT 59717 ; , Seattle, WA 98195"},{"name":"Department of Orthopedics and Sports Medicine, University of Washington , P.O. Box 173800 , Bozeman, MT 59717-3800 ; , Bozeman, MT 59717 ; , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"33","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"5","key":"2026082611340840800_bib1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/jor.1100070502","article-title":"Biosynthetic Response of Cartilage Explants to Dynamic Compression","volume":"7","year":"1989","journal-title":"J. Orthop. 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