Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud’s – Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Acroosteolysis (AO) secondary to bone resorption of distal phalanges affects up to 20% of systemic sclerosis (SSc) patients leading to shortening of the digits, impaired hand function, and disability. AO pathophysiology is not known, but chronic hypoxia secondary to SSc vasculopathy may be a contributing factor. In this study, we sought to define whether the propensity for osteoclast formation is increased in peripheral blood mononuclear cells (PBMCs) of SSc patients with AO compared to controls, and whether this may be associated with levels of the hypoxia-driven vascular endothelial growth factor (VEGF).
Methods:
PBMCs obtained from 26 SSc patients (11 with and 15 without AO) and 14 healthy controls were cultured in 96- well plates in the presence of receptor activator of nuclear factor-kappaB ligand (RANKL) and M-CSF. After 9 days, osteoclast-like tartrate resistant acid phosphatase (TRAP)-positive multinucleated giant cells (MNGs) were counted. MNGs formation was also assessed after VEGF (10 ng/ml) priming for 24 hours. Plasma VEGF levels were measured using an electrochemiluminescence platform (Meso Scale Discovery).
Results:
SSc patients with AO formed significantly more TRAP+ MNGs at day 9 than SSc patients without AO (142.4 ± 69.6 vs. 27.2 ± 17.6 MNG/well, P < 0.01), whereas no difference was noted between SSc without AO and controls (27.2 ± 17.6 MNG/well vs. 18.7 ± 27.0 MNGs/well, P=NS). Priming with VEGF at 10 ng/ml for 24 hours significantly increased TRAP+MNGs formation by 5.3 fold (P=0.002). In plasma of SSc patients with AO, VEGF levels were significantly higher than in SSc patients without AO (165.3 ± 80.2 vs. 88.1 ± 38.1 pg/ml, P<0.05). Strikingly, plasma VEGF levels correlated with TRAP+MNG formation (Spearman rho=0.386, P=0.05).
Conclusion:
AO is associated with an increased propensity of peripheral blood cells to form osteoclasts and this seems to be partly driven by higher VEGF plasma levels. Effective control of hypoxia and inhibition of terminal mediators of osteoclastogenesis may be an effective strategy to prevent and treat AO in SSc patients.
Disclosure:
J. K. Park,
None;
A. Fava,
None;
A. Rosen,
None;
F. Boin,
None.
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