{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:51:18Z","timestamp":1768816278714,"version":"3.49.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1148903"],"award-info":[{"award-number":["DGE-1148903"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["13\/RC\/2073s1"],"award-info":[{"award-number":["13\/RC\/2073s1"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Juvenile osteochondritis dissecans (JOCD) is a pediatric disease, which begins with an osteonecrotic lesion in the secondary ossification center which, over time, results in the separation of the necrotic fragment from the parent bone. JOCD predisposes to early-onset osteoarthritis. However, the knowledge gap in JOCD pathomechanisms severely limits current therapeutic strategies. To elucidate its etiology, we conducted a study with induced pluripotent stem cells (iPSCs) from JOCD and control patients. iPSCs from skin biopsies were differentiated to iMSCs (iPSC-derived mesenchymal stromal cells) and subjected to chondrogenic and endochondral ossification, and endoplasmic reticulum (ER)-stress induction assays. Our study, using 3 JOCD donors, showed that JOCD cells have lower chondrogenic capability and their endochondral ossification process differs from control cells; yet, JOCD- and control-cells accomplish osteogenesis of similar quality. Our findings show that endoplasmic reticulum stress sensing and response mechanisms in JOCD cells, which partially regulate chondrocyte and osteoblast differentiation, are related to these differences. We suggest that JOCD cells are more sensitive to ER stress than control cells, and in pathological microenvironments, such as microtrauma and micro-ischemia, JOCD pathogenesis pathways may be initiated. This study is the first, to the best of our knowledge, to realize the important role that resident cells and their differentiating counterparts play in JOCD and to put forth a novel etiological hypothesis that seeks to consolidate and explain previously postulated hypotheses. Furthermore, our results establish well-characterized JOCD-specific iPSC-derived in vitro models and identified potential targets which could be used to improve diagnostic tools and therapeutic strategies in JOCD.<\/jats:p>","DOI":"10.1093\/stcltm\/szad018","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T19:39:11Z","timestamp":1681760351000},"page":"293-306","source":"Crossref","is-referenced-by-count":3,"title":["Patient-Specific iPSC-Derived Models Link Aberrant Endoplasmic Reticulum Stress Sensing and Response to Juvenile Osteochondritis Dissecans Etiology"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1818-1260","authenticated-orcid":false,"given":"Giuliana E","family":"Salazar-Noratto","sequence":"first","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, GA , USA"},{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catriana C","family":"Nations","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hazel Y","family":"Stevens","sequence":"additional","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology , Atlanta, GA , USA"},{"name":"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maojia","family":"Xu","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, National University of Ireland Galway , Galway , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Gaynard","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, National University of Ireland Galway , Galway , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Dooley","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, National University of Ireland Galway , Galway , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nica","family":"de Nijs","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katya","family":"McDonagh","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, National University of Ireland Galway , Galway , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanbing","family":"Shen","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, National University of Ireland Galway , Galway , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S Clifton","family":"Willimon","sequence":"additional","affiliation":[{"name":"Children's Orthopaedics of Atlanta, Children\u2019s Healthcare of Atlanta , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Barry","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, National University of Ireland Galway , Galway , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E","family":"Guldberg","sequence":"additional","affiliation":[{"name":"Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology , Atlanta, GA , USA"},{"name":"George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, GA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"issue":"12","key":"2023051514374112100_CIT0001","doi-asserted-by":"crossref","first-page":"2325967118815846","DOI":"10.1177\/2325967118815846","article-title":"Demographics and Epidemiology of Osteochondritis Dissecans of the Elbow Among Children and Adolescents","volume":"6","author":"Kessler","year":"2018","journal-title":"Orthopaedic J Sports Med"},{"issue":"1","key":"2023051514374112100_CIT0002","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.cuor.2006.11.006","article-title":"Osteochondritis dissecans of the knee","volume":"21","author":"Schindler","year":"2007","journal-title":"Curr Orthop"},{"issue":"10","key":"2023051514374112100_CIT0003","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/j.1440-1827.2006.02015.x","article-title":"Osteochondritis dissecans of the elbow: histopathological assessment of the articular cartilage and subchondral bone with emphasis on their damage and repair","volume":"56","author":"Kusumi","year":"2006","journal-title":"Pathol Int"},{"issue":"7","key":"2023051514374112100_CIT0004","doi-asserted-by":"crossref","first-page":"232596711770464","DOI":"10.1177\/2325967117704644","article-title":"Nonoperative management of osteochondritis dissecans of the knee: progression to osteoarthritis and arthroplasty at mean 13-year follow-up","volume":"5","author":"Sanders","year":"2017","journal-title":"Orthopaedic J Sports Med"},{"issue":"5","key":"2023051514374112100_CIT0005","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1302\/2058-5241.4.180079","article-title":"Juvenile osteochondritis dissecans (JOCD) of the knee: current concepts review","volume":"4","author":"Masquijo","year":"2019","journal-title":"EFORT Open Rev"},{"issue":"5","key":"2023051514374112100_CIT0006","doi-asserted-by":"crossref","first-page":"297","DOI":"10.5435\/00124635-201105000-00007","article-title":"Diagnosis and treatment of osteochondritis dissecans","volume":"19","author":"Chambers","year":"2011","journal-title":"JAAOS- J Am Acad Orthop Surg"},{"issue":"2","key":"2023051514374112100_CIT0007","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.csm.2013.11.006","article-title":"Osteochondritis dissecands of the knee: Pathoanatomy, epidemiology, and diagnosis","volume":"33","author":"Grimm","year":"2014","journal-title":"Clin Sports Med"},{"key":"2023051514374112100_CIT0008","article-title":"Management of Osteochondritis Dissecans of the Knee","author":"Owens","year":"2009","journal-title":"Biologic Joint Reconstruction: Alternatives to arthroplasty"},{"key":"2023051514374112100_CIT0009","doi-asserted-by":"crossref","first-page":"3096","DOI":"10.1007\/s00167-020-06365-y","article-title":"The incidence and risk factors of osteoarthritis following osteochondritis dissecans of the knees: a systematic review and meta-analysis","volume":"29","author":"Tan","year":"2021","journal-title":"Knee Surg Sports Traumatol Arthrosc"},{"issue":"5","key":"2023051514374112100_CIT0010","first-page":"1121","article-title":"Juvenile Osteochondritis Dissecans: Is it a growth disturbance of the secondary physis of the epiphysis?","volume":"199","author":"Laor","year":"2012","journal-title":"Am J Reseach"},{"issue":"4","key":"2023051514374112100_CIT0011","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s11999-012-2619-6","article-title":"Osteochondritis dissecans knee histology studies have variable findings and theories of ethiology","volume":"471","author":"Shea","year":"2012","journal-title":"Clin Orthop Relat Res"},{"issue":"6","key":"2023051514374112100_CIT0012","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s00264-010-0951-6","article-title":"Viability of loose body fragments in osteochondritis dissecans of the knee. 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