Metabolic activity of osteoblasts retrieved from osteoarthritic patients after stimulation with mediators involved in periprosthetic loosening

Objective: To compare the effects of polymethylmetacrylate (PMMA), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) on osteoarthritic (OA) human osteoblasts (Ob). Methods: Ob cell cultures were prepared from metaphyseal trabecular bone of OA patients (n = 9). Their cellular metabolic activity was characterized by measuring alkaline phosphatase (ALPase), osteocalcin (Oc), osteoprotegerin (OPG), prostaglandin E2 (PGE2), IL-6, macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-κb ligand (sRANKL) in supernatants after Ob stimulation with PMMA, IL-1β, IL-6 or TNF-α. Results: IL-6 and PGE2 production by Ob was significantly increased by all mediators used. PMMA and TNF-α both stimulated M-CSF and sRANKL production whereas PMMA decreased and TNF-α augmented OPG release by Ob. The ratio sRANKL/OPG was significantly increased with PMMA and TNF-α, and treatment with anti-IL-6 antibodies did not alter this ratio. ALPase levels remained constant while only PMMA affected Oc production. Subclassification of patients into high or low endogenous producers of IL-6 and PGE2 before stimulation of Ob indicated that the two subgroups maintained similar responses to stimulation by all mediators. Conclusion: PMMA and TNF-α have comparable dual action on Ob, lowering their anabolic capacity and favoring production of bone resorption activators, an action not mediated by IL-6. This study confirms the important role of PMMA in implant loosening. However, the pertinence of high and low metabolic activities in OA Ob remains unclear, but could be involved in the pathophysiology of bone disease and aseptic loosening.