{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:45:17Z","timestamp":1784627117499,"version":"3.55.0"},"reference-count":19,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 109-2314-B-037-026, MOST108-2320-B-037-008 and MOST109-2320-B-037-005"],"award-info":[{"award-number":["MOST 109-2314-B-037-026, MOST108-2320-B-037-008 and MOST109-2320-B-037-005"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"publisher","award":["KMU-TP105B10 and KMU-DK105009"],"award-info":[{"award-number":["KMU-TP105B10 and KMU-DK105009"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011645","name":"Kaohsiung Medical University Chung-Ho Memorial Hospital","doi-asserted-by":"publisher","award":["KMUH105-5M30"],"award-info":[{"award-number":["KMUH105-5M30"]}],"id":[{"id":"10.13039\/501100011645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We recently reported that the chondrocyte-specific knockout of discoidin domain receptors 1 (Ddr1) delayed endochondral ossification (EO) in the growth plate by reducing the chondrocyte hypertrophic terminal differentiation, and apoptosis. The biologic and phenotypic changes in chondrocytes in the articular cartilage with osteoarthritis (OA) are similar to the phenomena observed in the process of EO. Additionally, autophagy can promote chondrocyte survival and prevent articular cartilage from degradation in OA. On this basis, we explored the effect of Ddr1 inhibition on OA prevention and further investigated the roles of autophagy in treating OA with a Ddr1 inhibitor (7 rh). The anterior cruciate ligament transection (ACLT)\u2013OA model was used to investigate the role of 7 rh in vivo. Forty 8-week-old mice were randomly assigned to four groups, including the sham group, ACLT group, and two treated groups (ACLT with 7 rh 6.9 nM or 13.8 nM). According to the study design, normal saline or 7 rh were intra-articular (IA) injected into studied knees 3 times per week for 2 weeks and then once per week for 4 weeks. The results showed that 7 rh treatment significantly improved the functional performances (the weight-bearing ability and the running endurance), decreased cartilage degradation, and also reduced the terminal differentiation markers (collagen type X, Indian hedgehog, and matrix metalloproteinase 13). Moreover, 7 rh decreased chondrocyte apoptosis by regulating chondrocyte autophagy through reducing the expression of the mammalian target of rapamycin and enhancing the light chain 3 and beclin-1 expression. These results demonstrated that the IA injection of 7 rh could reduce the chondrocyte apoptosis and promote chondrocyte autophagy, leading to the attenuation of cartilage degradation. Our observations suggested that the IA injection of 7 rh could represent a potential disease-modifying therapy to prevention OA progression.<\/jats:p>","DOI":"10.3390\/ijms21196991","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T09:28:08Z","timestamp":1600853288000},"page":"6991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Discoidin Domain Receptors 1 Inhibition Alleviates Osteoarthritis via Enhancing Autophagy"],"prefix":"10.3390","volume":"21","author":[{"given":"Hsin-Chaio","family":"Chou","sequence":"first","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8941-4792","authenticated-orcid":false,"given":"Chung-Hwan","family":"Chen","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Departments of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan"},{"name":"Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Division of Adult Reconstruction Surgery, Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Yin","family":"Chou","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7080-8652","authenticated-orcid":false,"given":"Tsung-Lin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-5604","authenticated-orcid":false,"given":"Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Chun","family":"Chuang","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shan","family":"Lin","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ling","family":"Ho","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Orthopedics, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8161-7472","authenticated-orcid":false,"given":"Yan-Hsiung","family":"Wang","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"School of Dentistry, College of Dental Medicine Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Yen","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Regeneration Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80708, 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