| First Author | Suhardi VJ | Year | 2024 |
| Journal | Nat Biomed Eng | Volume | 8 |
| Issue | 10 | Pages | 1285-1307 |
| PubMed ID | 39085645 | Mgi Jnum | J:374077 |
| Mgi Id | MGI:8255645 | Doi | 10.1038/s41551-024-01238-y |
| Citation | Suhardi VJ, et al. (2024) Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor. Nat Biomed Eng 8(10):1285-1307 |
| abstractText | 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. |
