# Potential molecular communication of blood and synovium through ligand-receptor interactions in osteoarthritis

## TL;DR

This study explores how blood and joint tissues communicate in osteoarthritis, revealing new molecular pathways that could lead to better treatments.

## Contribution

The paper identifies novel ligand-receptor interactions and molecular communication between blood and synovium in osteoarthritis.

## Key findings

- 129 ligands and 137 receptors in blood, and 108 ligands and 86 receptors in synovium were differentially expressed.
- Blood ligands were linked to inflammation and immunity, while synovium ligands were associated with angiogenesis.
- Immunofluorescence confirmed elevated IL6 and IL1B in OA synovium, suggesting systemic inflammation contributes to local disease.

## Abstract

Osteoarthritis (OA) is a common degenerative joint disease resulting from the breakdown of multiple joint tissues, remains a leading cause of disability with limited therapeutic options. Synovitis is one of the reasons of OA progression, while communication between blood and synovium during disease process is still unclear.

We used transcriptomic datasets from blood and synovium of healthy controls and OA patients to investigate potential molecular crosstalk between blood and synovium in OA pathogenesis through ligand-receptor pairs.

Ligand-receptor pair analysis revealed 129 ligands and 137 receptors differentially expressed in blood, and 108 ligands and 86 receptors in synovium. Gene ontology enrichment analysis of differentially expressed ligands indicated receptor ligand activity in both tissues, with blood enriched in leukocyte migration, cell chemotaxis, and leukocyte chemotaxis, and synovium in negative regulation of response to external stimulus, epithelial cell proliferation, and cell chemotaxis. Further protein-protein interaction (PPI) network analysis showed that blood ligands were mainly associated with inflammation and immunity (IL6, IL1B, IL23A, IFNA1, and TNF), while several synovium ligands were linked to angiogenesis (TGFB1, FGF7, and PDGFA). Based on ligand-receptor interactions and PPI network of differentially expressed ligands, we predicted and constructed molecular communication map between blood and synovium. Immunofluorescence staining of synovium showed more blood micro-vessels in OA patients and elevated IL6 and IL1B expression levels, suggesting that synovial inflammation might partly originate from pro-inflammatory cytokines in blood.

These findings offered new understanding of the molecular mechanisms underlying blood and synovium communication in OA, and provided potential therapeutic drug targets for OA treatment to simultaneously modulate systemic inflammation and local angiogenesis.