Targeting the CXCL12/CXCR4 pathway by an optimized derivative or EPI-X4 preserves chondrocyte function and offers a novel therapeutic approach in rheumatic diseases.

ABSTRACT:

Background

The C-X-C motif chemokine 12 (CXCL12) and its receptor CXCR4 are pivotal in tissue regeneration and inflammation, yet their role in osteoarthritis (OA) remains ambiguous. However, it is assumed that the CXCL12/CXCR4 axis likely contributes to OA progression through subchondral bone-cartilage crosstalk. This study compares the efficacy of the CXCR4 inhibitors AMD31000 and novel endogenous peptide inhibitors in human cartilage and isolated chondrocytes (hAC).

Methods

Human cartilage and hAC were obtained from OA patients undergoing arthroplasty. Expression of both CXCL12 receptors CXCR4 and ACKR3, were assessed by immunohistology and qRT-PRC. The effects of CXCR4 inhibitors, including AMD3100, EPI-X4, and its derivative EPI-X4 JM#21, were evaluated regarding cell vi

SUBMITTER: Ruths L 

PROVIDER: S-EPMC12670779 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature