Osteoclasts in Patients With PsA, RA Show Functional Differences

Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) osteoclasts show immune and other functional differences, according to the first human study that examined the detailed proteomic changes during human osteoclast differentiation. The results were published in Frontiers in Immunology.¹

“Our results shed light on the characteristic proteomic changes during human osteoclast differentiation and expression differences in RA and PsA, which reveal important pathophysiological insights in both diseases,” Orsolya Tünde Kovács, of Semmelweis University in Budapest, Hungary, and colleagues, explained.

PsA and RA are associated with increased activity of osteoclasts, which play an essential role in bone maintenance, repair, and remodeling. Inflammation may accelerate bone resorption via osteoclast activation and is associated with local and systemic bone loss in these inflammatory arthropathies. Little is understood about the molecular changes during human blood-derived osteoclast differentiation and there is no information about the differences in protein expression in osteoclasts derived from patients with PsA or RA.

Blood samples were collected from 6 healthy donors, 6 patients with PsA, and 6 patients with RA. Monocytes were isolated and differentiated into osteoclasts in vitro to analyze proteomic changes during osteoclast differentiation.

In healthy donor-derived monocytes, expression of the proteins involved in metabolic activity, secretory function, and cell polarity was increased during the differentiation of the osteoclasts, while signaling pathways involved in the immune functions were downregulated. The differences between cells of healthy donors and patients with PsA or PA were most pronounced after the final steps of differentiation to osteoclasts. Proteins involved in metabolic processes were decreased in PsA and RA osteoclasts compared with healthy samples. In PsA and RA osteoclasts, the expression of proteins involved in immunological processes and proteins of the major histocompatibility complex were increased compared with healthy osteoclasts. The processes involved in protein synthesis were downregulated in PsA osteoclasts, and the expression of proteins involved in ATP synthesis were decreased in RA samples.

In PsA and RA, the “differentiation to osteoclasts was characterized by decreased metabolic activity, associated with various immune pathway activities,” along with “accelerated cytokine production in RA,” the authors stated.

Further studies with a higher number of patients including different disease stages are needed to provide data regarding osteoclastogenesis in inflammatory arthropathies.

Still, in both PSA and RA, bone erosions may be present, although in PsA they may appear in both peripheral and axial joints and generally show asymmetric involvement, while in RA they mainly appear in peripheral joints and show symmetric involvement. “These bone erosions are in line with our results that suggest that osteoclasts in these diseases might keep some of their immune cell functions,” investigators concluded.

Reference:

Kovács OT, Tóth E, Ozohanics O, et al. Proteomic Changes of Osteoclast Differentiation in Rheumatoid and Psoriatic Arthritis Reveal Functional Differences. Front Immunol. 2022;13:892970. Published 2022 Jul 4. doi:10.3389/fimmu.2022.892970