{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:52:41Z","timestamp":1784854361120,"version":"3.55.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002855","name":"ministry of science and technology of the people\u2019s republic of china","doi-asserted-by":"publisher","award":["2019YFA0111900"],"award-info":[{"award-number":["2019YFA0111900"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Sports Med"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Doxycycline (Doxy) has been shown to facilitate tendon healing by reducing on-site matrix metalloproteinase (MMP) activity, but its effect on graft healing after anterior cruciate ligament reconstruction (ACLR) has not been investigated, and the therapeutic effect of Doxy in preventing ACLR-induced posttraumatic osteoarthritis (PTOA) is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis:<\/jats:title>\n                    <jats:p>Doxy promotes graft healing and alleviates the progression of PTOA after ACLR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design:<\/jats:title>\n                    <jats:p>Controlled laboratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Sprague Dawley rats (n = 74; age, 12-13 weeks; male) that underwent ACLR were divided into untreated control and Doxy treatment (50 mg\/kg\/d orally until sacrifice) groups. At 2 and 6 weeks after surgery, graft healing was assessed by biomechanical testing, histology, immunohistochemical staining, and micro\u2013computed tomography (\u03bcCT). The progression of PTOA was evaluated at 6 weeks by histology, the Mankin score, and immunofluorescence staining of the tibial plateau, and osteophyte formation was evaluated by \u03bcCT. Hindlimb weight distribution was evaluated at 6 weeks, and gait patterns were evaluated at 2 and 6 weeks. Intra-articular MMP activity was evaluated at 6 weeks in vivo using an MMP-activatable near-infrared fluorescent probe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Graft healing was enhanced by Doxy treatment, and the ultimate failure load (\n                      <jats:italic>P<\/jats:italic>\n                      = .002) and stiffness of the graft (\n                      <jats:italic>P<\/jats:italic>\n                      = .007) were significantly higher in the Doxy group at week 2. Bone mineral density and bone volume\/total volume for both the tibial and the femoral tunnels at week 6 in the Doxy group were significantly higher compared with in the control group (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05). The overall graft healing scores were significantly higher in the Doxy group. Doxy treatment enhanced graft integration, intratunnel graft integrity, and collagen birefringence; more collagen types 1 and 10 and less MMP-13 were found at the graft-bone interface. At week 6, the Doxy group had a lower modified Mankin score (\n                      <jats:italic>P<\/jats:italic>\n                      = .033) and showed fewer MMP 13\u2013positive chondrocytes at the articular cartilage surface (\n                      <jats:italic>P<\/jats:italic>\n                      = .002), indicating moderate joint cartilage damage. \u03bcCT revealed less osteophyte formation, and gait analysis revealed more symmetric weightbearing and gait patterns, after Doxy treatment at week 6 (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .05). In vivo imaging with the near-infrared fluorescent probe identified significantly lower intra-articular MMP activity in the Doxy group at week 6 (\n                      <jats:italic>P<\/jats:italic>\n                      = .016).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The oral administration of Doxy was able to synchronously promote graft healing and attenuate PTOA in an ACLR rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>Our results indicated that Doxy, a widely used drug, is potentially beneficial to patients after ACLR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03635465221145015","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T05:52:30Z","timestamp":1673848350000},"page":"461-475","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Doxycycline Promotes Graft Healing and Attenuates Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Reconstruction in a Rat Model"],"prefix":"10.1177","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-7856","authenticated-orcid":false,"given":"Mingde","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China"},{"name":"Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.Y.","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.H.","family":"Yung","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China"},{"name":"Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7475-3182","authenticated-orcid":false,"given":"Yangzi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine, Hong Kong Science Park, Hong Kong SAR, China"},{"name":"Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0363546506296043"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0363546509347366"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21122"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/0363546517730072"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/jisakos-2020-000451"},{"issue":"11","key":"e_1_3_3_7_2","first-page":"2401","article-title":"Enhancement of tendon-bone healing of anterior cruciate ligament grafts by blockage of matrix metalloproteinases","volume":"87","author":"Demirag B","year":"2005","unstructured":"Demirag B, Sarisozen B, Ozer O, Kaplan T, Ozturk C. 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