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Inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 on RANKL expression in fibroblast-like synoviocytes and osteoclast-like cell formation induced by IL-22 in rheumatoid arthritis
H. Wen1, Y. Liu2, J. Li3, D. Wei4, D. Liu5, F. Zhao6
- Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China. wenhongyan0509@aliyun.com
- Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
- Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
- Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
- Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
- Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China.
CER10829
2018 Vol.36, N°5
PI 0798, PF 0805
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PMID: 29465363 [PubMed]
Received: 19/09/2017
Accepted : 08/01/2018
In Press: 15/02/2018
Published: 26/09/2018
Abstract
OBJECTIVES:
To explore the inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 (l,25(OH)2D3) on receptor activator of nuclear factor-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLSs) and osteoclastogenesis induced by interleukin (IL)-22 in patients with rheumatoid arthritis (RA).
METHODS:
Fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLSs) were cultured and stimulated for RANKL expression with IL-22 in the absence or presence of various concentrations of l,25(OH)2D3, and JAK-2 inhibitor or p38 MAPK inhibitor at the optimised time point of IL-22 treatment. The level of RANKL messenger RNA (mRNA) or protein was measured using real-time polymerase chain reaction (RT-PCR) or western blot method. To assess the impact of l,25(OH)2D3 on osteoclastogenesis, isolated monocytes were activated by M-CSF and RANKL or cocultured with FLSs stimulated by IL-22 in the presence or absence of l,25(OH)2D3 and those inhibitors. TRAP-positive cells as differentiated osteoclasts were stained for alkaline phosphatase.
RESULTS:
FLSs stimulated with IL-22 for 72 hours were used in further experiment because of the highest expression of RANKL at this time point. The expression of RANKL mRNA and protein in IL-22-stimulated FLSs were significantly inhibited by 1 nM of 1,25(OH)2D3 (p<0.05). Interestingly, this inhibition was reversed by inhibitor of JAK-2/STAT-3 or p38 MAPK/NF-κB signalling. In monocytes cocultured with IL-22-stimulated FLSs in the presence of exogenous RANKL and M-CSF, 1,25(OH)2D3 could block the process of osteoclastogenesis by JAK-2/STAT-3 or p38 MAPK/NF-κB signalling.
CONCLUSIONS:
1,25(OH)2D3 may exert inhibitory effect on osteoclastogenesis of RA-FLSs by down-regulating RANKL expression, which could be mediated by IL-22 through JAK-2/STAT-3 and p38 MAPK/NF-κB signalling.
