{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:38:59Z","timestamp":1790091539918,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T00:00:00Z","timestamp":1460678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31271033"],"award-info":[{"award-number":["31271033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572098"],"award-info":[{"award-number":["81572098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation for Young Scientists of Shanxi Province, China","award":["2014021039-1"],"award-info":[{"award-number":["2014021039-1"]}]},{"name":"Innovation Foundation for Shanxi Province (China) Graduate Education","award":["2015SY32"],"award-info":[{"award-number":["2015SY32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cross-linked hyaluronic acid hydrogel (cHA gel) and dexamethasone (Dex) have been used to treat knee osteoarthritis (OA) in clinical practice owing to their chondroprotective and anti-inflammatory effects, respectively. The aim of the present study was to compare the treatment effects of the cHA gel pre-mixed with\/without Dex in a surgery-induced osteoarthritis model in rats. Anterior cruciate ligament transection (ACLT) surgery was performed on the right knee of rats to induce OA. Male 2-month-old Sprague-Dawley rats were randomly divided into five groups (n = 10\/per group): (1) ACLT + saline; (2) ACLT + cHA gel; (3) ACLT + cHA-Dex (0.2 mg\/mL) gel; (4) ACLT + cHA-Dex (0.5 mg\/mL) gel; (5) Sham + saline. Intra-joint injections were performed four weeks after ACLT in the right knee. All animals were euthanized at 12 weeks post-surgery. Cartilage damage and changes in the synovial membrane were assessed by micro X-ray, Indian ink articular surface staining, Safranin-O\/Fast Green staining, immunohistochemistry, hematoxylin and eosin staining of the synovial membrane, and quantitative reverse transcription-polymerase chain reaction for changes in gene expression. Micro X-ray revealed that the knee joint treated with the cHA-Dex gel was wider than those treated with cHA gel alone or saline. The cHA-Dex gel group had less Indian ink staining (indicator of cartilage fibrillation) than the cHA gel or saline injection groups. Safranin-O\/Fast Green staining indicated that increased proteoglycan staining and less cartilage damage were found in the cHA-Dex gel group compared with the cHA gel or saline injection groups. Quantification of histology findings from saline, cHA gel, cHA-Dex (0.2 mg\/mL) gel, cHA-Dex (0.5 mg\/mL) gel, and sham groups were 5.84 \u00b1 0.29, 4.50 \u00b1 0.87, 3.00 \u00b1 1.00, 2.00 \u00b1 0.48, and 0.30 \u00b1 0.58 (p &lt; 0.05), respectively. A strong staining of type II collagen was found in both the cHA-Dex gel groups compared with saline group or cHA alone group. Similar result was found for the mRNA level of aggrecan and opposite result for type X collagen. Hematoxylin and eosin staining in the synovial membrane showed less synovial lining cell layers and reduced inflammatory cell infiltration in cHA-Dex gel-treated animals compared with saline or cHA only groups. Altogether, cHA-Dex gel has better chondroprotective and anti-inflammatory effects in rat surgery-induced osteoarthritis than cHA alone.<\/jats:p>","DOI":"10.3390\/ijms17040411","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T11:36:02Z","timestamp":1460720162000},"page":"411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Intra-Articular Injection of Cross-Linked Hyaluronic Acid-Dexamethasone Hydrogel Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8811-0877","authenticated-orcid":false,"given":"Zhiwei","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Wei","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizong","family":"Gao","sequence":"additional","affiliation":[{"name":"BioRegen Biomedical (Changzhou) Co. Ltd., 167-5 East East Road, Changzhou 213025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Zhao","sequence":"additional","affiliation":[{"name":"BioRegen Biomedical (Changzhou) Co. Ltd., 167-5 East East Road, Changzhou 213025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"},{"name":"Department of Orthopedics, Warren Alpert Medical School of Brown University, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqing","family":"Duan","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcui","family":"Li","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wei","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, China"},{"name":"Department of Orthopedics, Warren Alpert Medical School of Brown University, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.joca.2015.03.009","article-title":"Oarsi clinical trials recommendations: Design and conduct of clinical trials for primary prevention of osteoarthritis by joint injury prevention in sport and recreation","volume":"23","author":"Emery","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00296-014-3175-z","article-title":"Potentially effective natural drugs in treatment for the most common rheumatic disorder: Osteoarthritis","volume":"35","author":"Farzaei","year":"2015","journal-title":"Rheumatol. 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