Department of Orthopedics and Department of Sports Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107# Yanjiang West Road, Guangzhou, Guangdong Province, 510120, China.
Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, #17 Lujiang Road, Hefei, Anhui Province, China.
BMC Musculoskelet Disord. 2024 Nov 21;25(1):942. doi: 10.1186/s12891-024-08068-8.
The global incidence of frozen shoulder (FS) (2% ~ 5%) and osteoporosis (OP) is high (9.1%-12.1%). Clinically, postmenopausal women are particularly at risk for both diseases. The main objective of this current research is to investigate the pathogenesis mechanism of FS and explore the connection between FS and OP.
We obtained FS and OP datasets from GEO and identified crosstalk genes. Following KEGG and GO enrich analysis, the p38 MAPK signaling pathway was focused and the specific p38α inhibitor TAK715 was screened out. We conducted flow cytometry, western blot, and PCR analyses to assess the treatment effect of TAK715 on FS synovium fibroblasts at different concentrations. Additionally, we employed SD rats to validate the treatment effects of TAK715 in vivo.
TAK715 was useful in reversing fibrosis at the concentration of 1 μM, 5 μM and 10 μM. The unbalanced apoptosis process in frozen shoulder cell and the activation of osteoclast were inhibited at the concentration of 5 μM by TAK715. Then we successfully established a FS and OP rat model, with the FS with OP rat displaying less range of motion (ROM) and thicker shoulder capsule. In FS rat that was treated with TAK715, the frozen shoulder side was corrected in ROM and bone loss.
The frozen shoulder with osteoporosis may exhibit more severe symptoms, and TAK715 is effective in protecting fibrosis and osteoporosis both in vitro and vivo. The therapy to correct FS and OP simultaneously by TAK715 provides novel approach in FS treatment and study.
全球冻结肩（FS）（2%~5%）和骨质疏松症（OP）的发病率很高（9.1%-12.1%）。临床上，绝经后妇女特别容易患这两种疾病。本研究的主要目的是探讨 FS 的发病机制，并探讨 FS 与 OP 之间的联系。
我们从 GEO 获得 FS 和 OP 数据集，并确定了串扰基因。进行 KEGG 和 GO 富集分析后，我们关注了 p38 MAPK 信号通路，并筛选出了特异性 p38α抑制剂 TAK715。我们通过流式细胞术、Western blot 和 PCR 分析评估了 TAK715 对不同浓度 FS 滑膜成纤维细胞的治疗效果。此外，我们还使用 SD 大鼠在体内验证 TAK715 的治疗效果。
TAK715 在 1μM、5μM 和 10μM 浓度下可有效逆转纤维化。TAK715 在 5μM 浓度下抑制了冻结肩细胞中不平衡的凋亡过程和破骨细胞的激活。然后，我们成功建立了 FS 和 OP 大鼠模型，OP 大鼠的 FS 模型显示出更小的运动范围（ROM）和更厚的肩囊。在接受 TAK715 治疗的 FS 大鼠中，ROM 中的冻结肩得到了纠正，并且骨丢失得到了改善。
骨质疏松症伴冻结肩可能表现出更严重的症状，TAK715 对体内外纤维化和骨质疏松症均有疗效。TAK715 通过同时纠正 FS 和 OP 的治疗方法为 FS 治疗和研究提供了新的方法。
