Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis.

Chuanlong Wu,Ruixin Sun,Fengxiang Liu,Zhiqing Liu,Yunhao Qin,Tingting Tang,Shengbing Yang,Xuqiang Liu,Zhenan Zhu,Degang Yu

doi:10.3389/fphar.2018.01291

Abstract

Joint replacement is essential for the treatment of serious joint disease. However, prosthetic failure remains an important clinical issue, with periprosthesis osteolysis (PO), caused by osteoclastic bone resorption induced by wear particles, being the leading cause of failure. Nuclear factor of activated T cells c1 (NFATc1) appears to play an important role in wear particle-induced osteoclastogenesis, with bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2, (SLC4A2) being upregulated during osteoclastogenesis in an NFATc1-dependent manner. Anion exchange mediated by SLC4A2 in osteoclasts could affect the bone resorption activity by regulating pHi. This study investigated the role and mechanism of SLC4A2 in wear particle-induced osteoclast differentiation and function in vitro. The use of 4, 4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS), an anion exchange inhibitor, suppressed wear particle-induced PO in vivo. Furthermore, controlled release of DIDS from chitosan microspheres can strengthen the PO therapy effect. Therefore, anion exchange mediated by osteoclastic SLC4A2 may be a potential therapeutic target for the treatment of aseptic loosening of artificial joints.

Highlights

Periprosthetic osteolysis (PO) and subsequent aseptic loosening remains a major problem for the long-term success and survival of prosthetic joints (Yang et al, 2004).Osteolysis induced by wear debris is an important concern considering that wear particles appear in tissues around a prosthesis in 70–90% cases (Baumann et al., 2004)
We wanted to know the expression of Slc4a2 in wear particle-induced osteoclastogenesis
We observed the effect of blocking Slc4a2 expression on PMMA particle-induced osteoclast differentiation

Summary

Introduction

Periprosthetic osteolysis (PO) and subsequent aseptic loosening remains a major problem for the long-term success and survival of prosthetic joints (Yang et al, 2004).Osteolysis induced by wear debris is an important concern considering that wear particles appear in tissues around a prosthesis in 70–90% cases (Baumann et al., 2004). Periprosthetic osteolysis (PO) and subsequent aseptic loosening remains a major problem for the long-term success and survival of prosthetic joints (Yang et al, 2004). Wear particles promote osteoclast differentiation and activation, which leads to bone loss around the prosthesis, accompanied by an increase in peripheral inflammatory mediators and dysfunction of osteoblasts, with the process. The 11R-VIVIT peptide (RRRRRRRRRRR-GGG-MAGPHPVIVITGPHEE) was obtained from Sigma Genosys (Woodlands, TX, United States). As the degradation of material, due to movement between the prosthetic components, is unavoidable, preventing the activation of osteoclasts, which is the direct cause of PO, could provide a therapeutic target to prevent PO and aseptic loosening of joint prostheses (Broomfield et al, 2017; Sartori et al., 2017)

Methods

Results

Conclusion