Abstract
Engineered biomaterials are envisioned to replace, augment, or interact with living tissues for improving the functional deformities associated with end-stage joint pathologies. Unfortunately, wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of Rankl in the conditioned medium collected from Ti particle–stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particle–treated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris–stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory osteolysis.
Highlights
Artificial joint replacements are a remarkably effective and safe method for treating patients with degenerative diseases such as osteoarthritis (OA) and inflammatory arthropathies, including rheumatoid arthritis (RA) (Mulhall et al, 2008; Shon et al, 2019)
To determine how Fibroblast-like synoviocytes (FLSs) might respond to Ti particle treatment, soluble proteins released in the culture medium were analyzed by the 312antibody–coated antibody array chip
The amounts of secretory protein level measurements were clustered as a percentage of total regulated proteins: 10.79% extracellular matrix, 11.80% cell migration, 11.23% cell differentiation, 5.18% cell cycle, 11.45% apoptotic process, 11.30% angiogenesis, 32.83% inflammatory and immune response, and 14.42% secretion by considering the signal intensity of soluble proteins released in the Ti condition medium (CM) to the control CM (Supplementary Figure S2C)
Summary
Artificial joint replacements are a remarkably effective and safe method for treating patients with degenerative diseases such as osteoarthritis (OA) and inflammatory arthropathies, including rheumatoid arthritis (RA) (Mulhall et al, 2008; Shon et al, 2019). Periprosthetic osteolysis is usually followed by aseptic loosening, which can be described as a failure of the implant due to poor initial fixation and mechanical damage to fixation over time or biological loss of fixation instigated by immunological reactions to wear debris particles (Gilbert et al, 2016). It is observed that 2–3 months after surgery, a fibrous membrane, irregularly organized (abundant in fibroblasts, macrophages, chondrocytes, lymphocytes, endothelial cells, mesenchymal stem cells (MSCs), and prosthesis-derived wear particles) and resembling more or less synovial tissue, may form around the bone/prosthesis interface (Zhang et al, 2010). There are still very few investigations that have addressed the possible role of other cell types in bone loss during periprosthetic osteolysis
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