The cellular and molecular mediators of peri-implant fibrosis—a most common reason for implant failure and for surgical revision after the replacement of a prosthetic joint—remain unclear. Here we show that peri-implant fibrotic tissue in mice and humans is largely composed of a specific population of skeletal cells expressing the leptin receptor (LEPR) and that these cells are necessary and sufficient to generate and maintain peri-implant fibrotic tissue. In a mouse model of tibial implantation and osseointegration that mimics partial knee arthroplasty, genetic ablation of LEPR⁺ cells prevented peri-implant fibrosis and the implantation of LEPR⁺ cells from peri-implant fibrotic tissue was sufficient to induce fibrosis in secondary hosts. Conditional deletion of the adhesion G-protein-coupled receptor F5 (ADGRF5) in LEPR⁺ cells attenuated peri-implant fibrosis while augmenting peri-implant bone formation, and ADGRF5 inhibition by the intra-articular or systemic administration of neutralizing anti-ADGRF5 in the mice prevented and reversed peri-implant fibrosis. Pharmaceutical agents that inhibit the ADGRF5 pathway in LEPR⁺ cells may be used to prevent and treat peri-implant fibrosis.

种植体周围纤维化的细胞和分子介质（种植体失败和更换假体关节后手术翻修的最常见原因）仍不清楚。在这里，我们表明小鼠和人类的种植体周围纤维化组织主要由表达瘦素受体 （LEPR） 的特定骨骼细胞群组成，并且这些细胞对于产生和维持种植体周围纤维化组织是必要且足够的。在模拟部分膝关节置换术的胫骨植入和骨结合小鼠模型中，LEPR⁺ 细胞的基因消融可防止种植体周围纤维化，并且从种植体周围纤维化组织植入 LEPR⁺ 细胞足以诱导次级宿主纤维化。LEPR⁺ 细胞中粘附 G 蛋白偶联受体 F5 （ADGRF5） 的条件性缺失减轻了种植体周围纤维化，同时增加了种植体周围骨形成，并且通过关节内或全身施用中和抗 ADGRF5 抑制了小鼠的种植体周围纤维化。抑制 LEPR⁺ 细胞中 ADGRF5 通路的药物可用于预防和治疗种植体周围纤维化。