TNF-α Activating Osteoclasts in Patients with Psoriatic Arthritis Enhances the Recruitment of Osteoclast Precursors: A Plausible Role of WNT5A-MCP-1 in Osteoclast Engagement in Psoriatic Arthritis

Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-alpha blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-alpha milieu in PsA. We first profiled the expression of WNT ligands in CD14(+) monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-alpha exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-alpha in MDOC from PsA patients. The number of CD68(+)WNT5A(+) osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-alpha but not IL-17. We conclude that TNF-alpha recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.

Automated summary

In psoriatic arthritis, TNF-alpha recruits osteoclast precursors by increasing MCP-1 production but does not directly activate osteoclastogenesis.