<em>Schistosoma japonicum</em> cystatin suppresses osteoclastogenesis via manipulating the NF‑κB signaling pathway

Chen,Yu; Wei,Bangguo; Xu,Panpan; Tang,Huadong; Yang,Langlang; Wang,Yuhang; Fu,Yingxiao; Yang,Xiaodi; Mao,Yingji

doi:10.3892/mmr.2021.11912

Schistosoma japonicum cystatin suppresses osteoclastogenesis via manipulating the NF‑κB signaling pathway

Authors:
- Yu Chen
- Bangguo Wei
- Panpan Xu
- Huadong Tang
- Langlang Yang
- Yuhang Wang
- Yingxiao Fu
- Xiaodi Yang
- Yingji Mao
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Affiliations: School of Life Sciences, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Key Laboratory of Anhui Province for Tissue Transplantation, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Microbiology and Parasitology, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
Published online on: February 9, 2021 https://doi.org/10.3892/mmr.2021.11912
Article Number: 273
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abnormal osteoclastic activation and secretion of cysteine proteinases result in excessive bone resorption, which is one of the primary factors in the development of bone metabolic disorders, such as rheumatoid arthritis and osteoporosis. Mammalian cystatins have been demonstrated to restrain osteoclastic bone resorption and to alleviate severe osteolytic destruction via blocking the activity of cysteine proteinases. However, the specific effects of parasite cystatins on the formation and function of osteoclasts remain unclear. The purpose of the current study was to explore the effects of cystatins from Schistosoma japonicum (Sj‑Cys) on macrophage colony‑stimulating factor (M‑CSF) and receptor activator of NF‑κB ligand (RANKL)‑induced osteoclast differentiation, as well as the underlying molecular mechanisms. Recombinant Sj‑Cys (rSj‑Cys) dose‑dependently restrained osteoclast formation, with a half‑maximal inhibitory concentration (IC₅₀) value of 0.3 µM, and suppressed osteoclastic bone resorptive capability in vitro. The findings were based on tartrate resistant acid phosphatase (TRAP) staining and bone resorption assays, respectively. However, the cell viability assay showed that the repression of rSj‑Cys on osteoclast formation did not depend on effects on cell viability or apoptosis. Based on the results of reverse transcription‑quantitative PCR and western blot analysis, it was found that rSj‑Cys downregulated the expression levels of osteoclastogenesis‑related genes and proteins, by interfering with M‑CSF and RANKL‑induced NF‑κB signaling and downstream transcription factors during early‑phase osteoclastogenesis. Overall, the results of the present study revealed that rSj‑Cys exerted an inhibitory role in osteoclast differentiation and could be a prospective biotherapeutic candidate for the treatment and prevention of bone metabolic disorders.

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