[The role and mechanism of chemokine network in promoting osteoarthritis progression by regulating synovial macrophage heterogeneity].

OBJECTIVE

To review the role of chemokine networks in regulating synovial macrophage heterogeneity during osteoarthritis (OA) pathogenesis.

METHODS

A review of recent literature on the developmental origins of OA synovial macrophages, single-cell transcriptomic characteristics, and chemokine signaling pathways was conducted to systematically summarize the functional phenotypes, immunometabolic mechanisms, and regulatory roles of synovial macrophages in OA.

RESULTS

OA has been established as a low-grade, chronic inflammatory disease affecting the entire joint. Single-cell and spatial transcriptomic studies have confirmed that synovial macrophages are not a single population but rather a dynamic continuum of different functional states, including steady-state barrier-like, inflammatory amplification, fibrosis-related, and lipid-enriched phenotypes. Chemokine networks play a dual crucial role in this process: on one hand, chemokine gradients guide the migration of peripheral monocytes to the synovium and influence their differentiation; on the other hand, synovial macrophages in different states secrete chemokines, mediating transcellular communication between the synovium, subchondral bone, and peripheral nerves. This process reshapes the microenvironment and amplifies local inflammation and pain signals. Current therapeutic strategies targeting macrophage metabolic reprogramming and chemokine axis blockade show potential clinical applications.

CONCLUSION

Re-examining the interaction between synovial macrophages and microenvironment and constructing an integrated perspective of "lineage-state-chemokine network" will help to understand the pathological progression mechanism of OA. In the future, it is expected to provide a theoretical framework and intervention targets for the precise immune regulation of OA and the development of new targeted drugs by accurately analyzing the spatiotemporal evolution of macrophage subsets and their interaction with chemokines.