Donat Antonia, Xie Weixin, Jiang Shan, Brylka Laura Janina, Schinke Thorsten, Rolvien Tim, Frosch Karl-Heinz, Baranowsky Anke, Keller Johannes
Department of Trauma and Orthopedic Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251, Hamburg, Germany.
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.
Inflamm Res. 2025 Mar 6;74(1):48. doi: 10.1007/s00011-025-02013-8.
Osteoarthritis (OA) is one of the leading causes of disability in the aging population. While about 10% of the adult population is affected by OA, there is to date no curative treatment and joint replacement surgery remains the only option for treating end-stage OA. Previous studies found elevated levels of the chemokine C-X-C motif ligand 9 (CXCL9) in the synovial fluid of OA knees. However, the exact role of CXCL9 in OA progression is still unknown.
Female wild-type and Cxcl9-deficient mice were challenged with a unilateral anterior cruciate ligament transection (ACLT). Joint destruction in early and late stages of experimental OA was assessed using micro-CT scanning, histological scoring, histomorphometry, and gene expression analysis.
Inactivation of Cxcl9 protected from cartilage destruction and osteophyte formation in post-traumatic OA in mice. Similarly, indices of joint inflammation including synovitis and expression of pro-inflammatory interleukin-1beta were reduced in OA knees of Cxcl9-deficient mice. However, bone erosion and pathophysiological changes in the subchondral bone compartment remained unaffected in Cxcl9-deficient mice with experimental OA.
Our results point towards a pro-inflammatory role of CXCL9 in OA and identify a potential new target for the pharmacological treatment of OA.
骨关节炎（OA）是老年人群致残的主要原因之一。虽然约10%的成年人口受OA影响，但迄今为止尚无治愈方法，关节置换手术仍是治疗终末期OA的唯一选择。先前的研究发现，OA膝关节滑液中趋化因子C-X-C基序配体9（CXCL9）水平升高。然而，CXCL9在OA进展中的确切作用仍不清楚。
对雌性野生型和Cxcl9基因缺陷型小鼠进行单侧前交叉韧带横断术（ACLT）。使用微型计算机断层扫描、组织学评分、组织形态计量学和基因表达分析评估实验性OA早期和晚期的关节破坏情况。
Cxcl9失活可保护小鼠免受创伤后OA的软骨破坏和骨赘形成。同样，Cxcl9基因缺陷型小鼠OA膝关节的关节炎症指标（包括滑膜炎）和促炎白细胞介素-1β的表达均降低。然而，实验性OA的Cxcl9基因缺陷型小鼠的骨侵蚀和软骨下骨区的病理生理变化未受影响。
我们的结果表明CXCL9在OA中具有促炎作用，并确定了OA药物治疗的一个潜在新靶点。
