Intra-Articular Injection of Cross-Linked Hyaluronic Acid-Dexamethasone Hydrogel Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis.
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 ± 0.29, 4.50 ± 0.87, 3.00 ± 1.00, 2.00 ± 0.48, and 0.30 ± 0.58 (p < 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.
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. joeyzhangzhiwei@163.com.
Zhiwei
Z
Zhang
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. weixiaochun11@126.com.
Xiaochun
X
Wei
BioRegen Biomedical (Changzhou) Co. Ltd., 167-5 East East Road, Changzhou 213025, China. jzgao@bioregenmed.com.
Jizong
J
Gao
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. zhaoyu20806@163.com.
Yu
Y
Zhao
BioRegen Biomedical (Changzhou) Co. Ltd., 167-5 East East Road, Changzhou 213025, China. ymzhao@bioregenmed.com.
Yamin
Y
Zhao
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. guol0918@126.com.
Li
L
Guo
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. chenchongwei.ty@163.com.|Department of Orthopedics, Warren Alpert Medical School of Brown University, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA. chenchongwei.ty@163.com.
Chongwei
C
Chen
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. ncbivip@163.com.
Zhiqing
Z
Duan
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. lpc1977@163.com.
Pengcui
P
Li
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. lei_wei@brown.edu.|Department of Orthopedics, Warren Alpert Medical School of Brown University, Suite 402A, 1 Hoppin Street, Providence, RI 02903, USA. lei_wei@brown.edu.
Lei
L
Wei
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D024043:Collagen Type II / Q000235:genetics; D003432:Cross-Linking Reagents; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D020100:Hydrogels / Q000737:chemistry*; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects; D008297:Male; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D003432:Cross-Linking Reagents; D020100:Hydrogels; D003907:Dexamethasone; D006820:Hyaluronic Acid
cross-linked hyaluronic acid; dexamethasone; intra-articular injection; osteoarthritis