Abstract
Osteoporosis is a major skeletal disorder characterized by reduced bone strength and increased risk of fractures. Excessive osteoclast-mediated bone resorption is a primary cause of this condition, underscoring the need for effective anti-resorptive therapies. N-phenyl-methylsulfonamido-acetamide (PMSA) compounds have been previously identified as potential anti-resorptive agents that inhibit osteoclastogenesis. In this study, ribonucleic acid (RNA)-sequencing and proteomic analyses identified calcineurin (CaN) as a potential target of PMSA implicated in osteoclast differentiation. PMSA bound to CaN and suppressed its phosphatase activity, which is essential for the activation and translocation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), a key regulator of osteoclastogenesis. PMSA treatment resulted in altered NFATc1-related signaling and increased phospho-NFATc1 levels in osteoclasts. Overall, these findings suggest that PMSA may inhibit CaN activity during osteoclast differentiation, positioning it as a promising therapeutic candidate for osteoporosis.
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Data availability
The datasets generated and analyzed during the current study are available at the Gene Expression Omnibus site of the NCBI; PRJNA1396781 https://dataview.ncbi.nlm.nih.gov/object/PRJNA1396781?reviewer=if3f02ghqv4hia1dh6q5f1g76h
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Funding
This work was supported by the National Research Foundation of Korea (NRF) grant, funded by the Korean government (MSIT) (RS-2023–00214202 and RS-2025–00557481).
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Study Design: E.C., D.K.C., H.Y., C.P., and T.-H.L. Experimental Execution: E.C., S.C. Data Analysis: E.C., S.C., C.P., Manuscript preparation and Writing: E.C. All authors critically reviewed and approved the final manuscript.
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Cho, E., Cheon, S., Choi, D.K. et al. PMSA as a potential modulator of calcineurin phosphatase activity. Sci Rep (2026). https://doi.org/10.1038/s41598-026-48882-9
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DOI: https://doi.org/10.1038/s41598-026-48882-9
