Osteoclastogenic Cytokine Secretion in Response to Calcitriol in PsA

Recent data confirmed altered bone turnover in psoriatic arthritis (PsA) patients, and demonstrated increased osteoclastogenic potential and proinflammatory cytokine secretion capacity of certain peripheral blood mononuclear cells (PBMCs) compared with psoriasis vulgaris (PsV) and patients in a healthy control group.¹

Vitamin D is a key factor in calcium homeostasis, bone formation, osteoclastogenesis, and the regulation of immune response. Therefore, researchers examined osteoclast differentiation and cytokine secretion of PBMCs in patients with PsV and PsA in response to 1,25(OH)₂D₃.

Researchers measured the serum levels of bone turnover markers with enzyme-linked immunosorbent assays in patients with PsV and PsA, comparing them against healthy controls. They isolated and cultured PBMCs with or without receptor activator of nuclear factor kappa-B ligand (RANKL)/macrophage-colony stimulating factor (M-CSF) and 1,25(OH)₂D_3, and assessed osteoclast differentiation and cytokine secretion.

Overall, PsA patients had lower osteocalcin serum levels (P=.011), and had higher C-telopeptide of type I collagen (CTX-1) serum levels (P=.002) compared to patients with PsV and the healthy controls. cathespin K serum levels were also higher in patients with PsA compared with patients with PsV (P=.028).

The investigators also noted that levels of degradation product per enzyme of cathespin K (CTX-1/ cathespin K ratios) were significant in PsA patients compared with healthy controls (P=.002).

In addition, PBMCs stimulated with RANKL/M-CSF from PsA patients produced higher proinflammatory cytokine levels. These PBMCs also had a differential secretion profile in response to 1,25(OH)₂D₃ compared with PBMCs from PsV patients and healthy controls.

“Our data provides new insight into the different cytokine secretion profiles of PBMCs in the circulation of patients with PsA and PsV, and differences in their capacity to differentiate into osteoclasts and respond to 1,25(OH)₂D₃,” the authors wrote in their study, published in Plos One. “Therefore, these data also suggest the development of therapeutic strategies including vitamin D for patients with psoriatic arthritis.”

Summary and Clinical Applicability

The study confirmed an altered bone remodeling in patients with PsA characterized by lower serum osteocalcin, and higher cathespin K, CTX-1, CTX-1/ osteocalcin, and CTX-1/cathespin K compared with patients with PsV and controls.

“Our results showed a negative high coefficient correlation between CT and CTSK [cathespin K] serum levels in patients with PsA but no correlation in case of PsV and healthy controls,” the authors added. “It is known that CT inhibits bone resorption in response to hypercalcemic serum conditions which might explain partially an increase in the degradation of type 1 collagen by CTSK in the case of patients with PsA.”

These results suggest there may be potential for therapeutic intervention with 1,25(OH)2D3 by taking into account the variations in PBMC cytokine secretion profiles and osteoclastic differentiation. 

Reference

1.  Cubillos S, Krieg N, Norgauer J. Effect of vitamin D on peripheral blood mononuclear cells from patients with psoriasis vulgaris and psoriatic arthritis. Plos One. 2016;11(4): doi: 10.1371/journal.pone.0153094.