Department of Orthopedics, Chengdu Second People's Hospital, Chengdu, 610017, China.
J Orthop Surg Res. 2022 Jul 6;17(1):343. doi: 10.1186/s13018-022-03224-z.
Ankylosing spondylitis (AS) is a refractory autoimmune disease, whose typical pathology is the development of inflammation to ossification and ankylosis. Histone deacetylase 1 (HDAC1) is considered to be a key factor involved in inflammatory gene transduction, but its role in AS remains unclear. The purpose of this study was to explore the role and possible mechanism of HDAC1 in AS based on the Wnt-Smad pathway. Fibroblasts were isolated from hip synovial tissues of AS patients, adeno-associated virus (AAV) was used to regulate the expression of HDAC1, DKK-1 and SIS3 was used to inhibit Wnt and Smad, respectively. The expressions of Wnt-Smad pathway-related proteins were analyzed by WB, and the TRP ion channel proteins were analyzed by immunofluorescence and WB. The proliferation of AS fibroblasts was detected by CCK-8, the expression of inflammatory cytokines was detected by ELISA, and the effects of HDAC1 on osteogenic differentiation of AS fibroblasts were investigated by alkaline phosphatase (ALP) activity, intracellular calcium concentration, mineralization and osteogenic proteins expressions. Results showed that HDAC1 significantly affected the protein expressions of the Wnt-Smad pathway in AS fibroblasts, and Wnt inhibitor DKK-1 and Smad3 inhibitor SIS3 could significantly reverse the effect of HDAC1 on the Wnt-Smad pathway. In addition, HDAC1 significantly activated the TRP ion channel and promoted the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts. DKK-1 or SIS3 treatment significantly inhibit the effect of HDAC-1 on AS fibroblasts, suggesting that the Wnt-Smad pathway is involved in the regulation of AS by HDAC1. In conclusion, HDAC1 promotes the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts through the Wnt-Smad pathway.
强直性脊柱炎（AS）是一种难治性自身免疫性疾病，其典型病理学为炎症向骨化和强直发展。组蛋白去乙酰化酶 1（HDAC1）被认为是参与炎症基因转导的关键因素，但它在 AS 中的作用尚不清楚。本研究旨在基于 Wnt-Smad 通路探讨 HDAC1 在 AS 中的作用及可能机制。分离 AS 患者髋关节滑膜组织中的成纤维细胞，用腺相关病毒（AAV）调节 HDAC1 的表达，用 DKK-1 和 SIS3 分别抑制 Wnt 和 Smad。用 WB 分析 Wnt-Smad 通路相关蛋白的表达，用免疫荧光和 WB 分析 TRP 离子通道蛋白的表达。用 CCK-8 检测 AS 成纤维细胞的增殖，用 ELISA 检测炎症细胞因子的表达，用碱性磷酸酶（ALP）活性、细胞内钙离子浓度、矿化和骨形成蛋白表达检测 HDAC1 对 AS 成纤维细胞成骨分化的影响。结果表明，HDAC1 显著影响 AS 成纤维细胞中 Wnt-Smad 通路的蛋白表达，Wnt 抑制剂 DKK-1 和 Smad3 抑制剂 SIS3 可显著逆转 HDAC1 对 Wnt-Smad 通路的作用。此外，HDAC1 显著激活 TRP 离子通道，促进 AS 成纤维细胞的增殖、炎症反应和成骨分化。DKK-1 或 SIS3 处理可显著抑制 HDAC-1 对 AS 成纤维细胞的作用，提示 Wnt-Smad 通路参与了 HDAC1 对 AS 的调控。综上所述，HDAC1 通过 Wnt-Smad 通路促进 AS 成纤维细胞的增殖、炎症反应和成骨分化。
