{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:01:55Z","timestamp":1792789315982,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T00:00:00Z","timestamp":1548028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme under Marie Sklodowska-Curie","award":["721432"],"award-info":[{"award-number":["721432"]}]},{"name":"German Society for Orthopaedics and Orthpaedic Surgery","award":["Verbund-Hexosaminpathway"],"award-info":[{"award-number":["Verbund-Hexosaminpathway"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a progressive joint disease characterized by a continuous degradation of the cartilage extracellular matrix (ECM). The expression of the extracellular glycoprotein thrombospondin-4 (TSP-4) is known to be increased in injured tissues and involved in matrix remodeling, but its role in articular cartilage and, in particular, in OA remains elusive. In the present study, we analyzed the expression and localization of TSP-4 in healthy and OA knee cartilage by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblot. We found that TSP-4 protein expression is increased in OA and that expression levels correlate with OA severity. TSP-4 was not regulated at the transcriptional level but we detected changes in the anchorage of TSP-4 in the altered ECM using sequential protein extraction. We were also able to detect pentameric and fragmented TSP-4 in the serum of both healthy controls and OA patients. Here, the total protein amount was not significantly different but we identified specific degradation products that were more abundant in sera of OA patients. Future studies will reveal if these fragments have the potential to serve as OA-specific biomarkers.<\/jats:p>","DOI":"10.3390\/ijms20020447","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T03:08:22Z","timestamp":1548126502000},"page":"447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Expression of Thrombospondin-4 Correlates with Disease Severity in Osteoarthritic Knee Cartilage"],"prefix":"10.3390","volume":"20","author":[{"given":"Kathrin","family":"Maly","sequence":"first","affiliation":[{"name":"Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstra\u00dfe 2, 60528 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Schaible","sequence":"additional","affiliation":[{"name":"Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstra\u00dfe 2, 60528 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Riegger","sequence":"additional","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedics, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf E.","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedics, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Meurer","sequence":"additional","affiliation":[{"name":"Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstra\u00dfe 2, 60528 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9354","authenticated-orcid":false,"given":"Frank","family":"Zaucke","sequence":"additional","affiliation":[{"name":"Dr. Rolf M. 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