Background Previously, immunity to protein phosphatase magnesium-dependent 1A (PPM1A), which was associated with TGF-β signaling, was reported in patients with ankylosing spondylitis (AS). In addition, PPM1A plays an important role in promotion of osteoblast (OB) differentiation.
Objectives We try to investigate the role of PPM1A in osteoclast (OC) differentiation, given that AS was associated with OC activation as well as OB differentiation.
Methods The expression of PPM1A was evaluated in bone-marrow macrophage during OC differentiation after stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL). To know the role of PPM1A in OC differentiation, OC differentiation was determined by tartrate-resistant acid phosphatase staining after with or without PPM1A knockdown by siRNA. Further, RANK expression and NF-kB signaling were investigated to see whether RANKL/RANK pathway is responsible for the effects of PPM1A in osteoclastogenesis.
Results During OC differentiation, PPM1A expression was up-regulated with M-CSF and RANKL stimulation after three days in culture. In addition, RANKL-induced osteoclastogenesis was significantly attenuated by knockdown of PPM1A. However, PPM1A-mediated effects on OC differentiation were not observed when RANK signaling was already triggered before knockdown of PPM1A. Further, we found that silencing of PPM1A showed decrease in RANK expression and increase in IkB expression, indicating the enhancement of RANK/NF-kB pathway by PPM1A.
Conclusions Our present findings suggested that PPM1A plays an important role in OC differentiation through enhancement of RANK and NF-kB signaling.
Role of Protein Phosphatase Magnesium-Dependent 1A and Anti–Protein Phosphatase Magnesium-Dependent 1A Autoantibodies in Ankylosing Spondylitis. Arthritis and Rheumatology, 66(10), 2793-2803, 2014
Disclosure of Interest None declared