PMID- 38418169 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20240301 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 104 IP - 9 DP - 2024 Mar 5 TI - [Study on the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogelin post-traumatic osteoarthritis]. PG - 695-703 LID - 10.3760/cma.j.cn112137-20231008-00672 [doi] AB - Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1beta, IL-6, TNF-alpha, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34+/-0.35, and it was 1.17+/-0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66+/-0.41 vs 0.22+/-0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 beta, IL-6, TNF-alpha, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60+/-0.07 vs 6.63+/-0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex. FAU - Zhang, Z W AU - Zhang ZW AD - Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Zhao, J Y AU - Zhao JY AD - Department of Endocrinology, Taiyuan People's Hospital, Taiyuan 030001, China. FAU - Feng, Y AU - Feng Y AD - Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Yin, K AU - Yin K AD - Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Li, P C AU - Li PC AD - Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China. FAU - Wei, X C AU - Wei XC AD - Shanxi Key Laboratory of Bone and Soft Tissue Injury Repair, Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China. LA - chi GR - U21A20353, 82172503/National Natural Science Foundation of China/ GR - 20210302124192/Natural Science Foundation for Young Scholars of Shanxi Province/ GR - J20220335/Teaching Reformation and Innovation Foundation for University of Shanxi Province/ GR - 2023ZYYC2038/Foundation of Shanxi Provincial Administration of Traditional Chinese Medicine/ GR - 202202‑05/Science Foundation for Young Scholars of the Second Hospital of Shanxi Medical University/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 9004-61-9 (Hyaluronic Acid) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 7S5I7G3JQL (Dexamethasone) RN - 0 (Hydrogels) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - Rats MH - Animals MH - Hyaluronic Acid/pharmacology MH - Matrix Metalloproteinase 3/pharmacology MH - Matrix Metalloproteinase 13/metabolism/pharmacology MH - Interleukin-6 MH - Tumor Necrosis Factor-alpha/metabolism MH - Rats, Sprague-Dawley MH - *Osteoarthritis/metabolism MH - *Cartilage, Articular/metabolism/pathology MH - Inflammation MH - Chondrocytes MH - Dexamethasone/pharmacology MH - Hydrogels/pharmacology MH - RNA, Messenger EDAT- 2024/02/29 00:43 MHDA- 2024/03/01 06:45 CRDT- 2024/02/28 21:09 PHST- 2024/03/01 06:45 [medline] PHST- 2024/02/29 00:43 [pubmed] PHST- 2024/02/28 21:09 [entrez] AID - 10.3760/cma.j.cn112137-20231008-00672 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2024 Mar 5;104(9):695-703. doi: 10.3760/cma.j.cn112137-20231008-00672.