The aim of this study was to identify inflammatory mediators of potential clinical relevance in synovial fluid (SF) samples of patients with knee osteoarthritis (OA). Therefore, radiographic OA severity, knee pain and function of 34 OA patients undergoing unicompartmental (UC) and bicompartmental (BC) knee arthroplasty were assessed prior to surgery and SF samples were analyzed for a broad variety of inflammatory mediators, including interleukins (ILs), interferons (IFNs), C-X-C motif ligand chemokines (CXCLs), and growth factors (nerve growth factor; NGF, vascular endothelial growth factor; VEGF, and stem cell growth factor β; SCGF-β) using multiplex assay. Significant differences were observed between the SF levels of different inflammatory markers. When compared to UC OA, significantly higher concentrations of IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, VEGF and CXCL1 were detected in BC OA. Correlation analyses revealed significant associations between OA severity and IL-6, IL-8, IFN-γ, SCGF-β, VEGF, CXCL1. Interestingly, increases in both anti- (IL-10, IL-13) and pro-inflammatory (IL-7, IL-12, IFN-γ) cytokines, as well as growth factors (SCGF-β, VEGF), correlated significantly with the level of knee pain. Poorer knee function was associated with higher IL-6, IL-10, IL-12, IL-13, IL-18, βNGF, SCGF-β, VEGF and CXCL9 levels. In conclusion, this study provides an extensive profile of synovial inflammatory mediators in knee OA and identifies cytokines of potential clinical relevance. In fact, five of the mediators examined (IL-10, IL-12, IL-13, SCGF-β, VEGF) significantly correlate with both knee pain and function.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet

Despite the growing body of literature demonstrating a crucial role of T helper cell (Th) responses in the pathogenesis of osteoarthritis (OA), only few clinical studies have assessed interactions between Th cells and OA—related symptoms. Yet, the inclusion of clinical data in the interpretation of cellular analyses of Th cell infiltration is essential to reveal the mechanisms underlying the complex pathophysiology of OA pain and disability. Thus, the aim of the study was to analyze the infiltration pattern of Th cells in systemic (peripheral blood) and joint-derived (synovial membrane and fluid) samples from patients with knee OA in relation to OA-induced pain and disability. Therefore, radiographic OA severity, knee pain and function of 47 OA patients undergoing knee arthroplasty were evaluated prior to surgery. In parallel, samples of peripheral blood (PB), synovial membrane (SM) and synovial fluid (SF) were harvested and analyzed for different Th subsets using flow cytometry. According to surface marker expression Th cells (CD3⁺ CD4⁺ CD8⁻) were assigned to the Th subsets Th1 (CXCR3⁺, CCR5⁺), Th2 (CCR3⁺, CCR4⁺) and Th17 (CD161⁺, CCR6⁺). Interestingly, infiltration of the SM with all Th subtypes (Th1, Th2, Th17) significantly correlated with OA-induced disability. Most importantly, synovial CCR5⁺ and CCR3⁺ Th cell infiltration was associated with OA-related knee pain and disability. Furthermore, higher percentage rates of CXCR3⁺ Th cells in all tissue samples (PB, SM, SF) showed significant associations with OA severity. In contrast, increasing percentage rates of CD161⁺ Th cells in SM samples corresponded to a better functional outcome. In conclusion, the current study provides an extensive profile of the Th cell infiltration pattern in PB, SF and SM from patients with clinically relevant knee OA. Th cell infiltration of the SM might play a crucial role not only in the pathogenesis of OA but also in the development of OA-related knee pain and disability.

Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional disability really is, remains elusive. Thus, the aim of the current study was to characterize the infiltration profile of Tregs in systemic (peripheral blood) and joint-derived (synovial fluid and synovial membrane) samples from patients with knee OA in relation to OA-induced symptoms. To this end, Treg infiltration (CD4⁺CD25^+/high CD127^low/−) was analyzed in matched samples of peripheral blood (PB), synovial fluid (SF) and synovial membrane (SM) from a total of 47 patients undergoing elective knee arthroplasty using flow cytometry. At the same time, knee pain and function were assessed and correlated with Treg proportions in different compartments (PB, SF, SM). Interestingly, matched-pair analysis revealed significantly higher Treg proportions in joint-derived samples than in PB, which was mainly attributed to the high Treg frequency in SF. Moreover, we found significant associations between infiltrating Tregs and OA-related symptoms which indicate that lower Treg proportions—especially in the SM—are related to increased pain and functional disability in knee OA. In conclusion, this study highlights the importance of local cellular inflammatory processes in OA pathology. Intra-articular Treg infiltration might play an important role not only in OA pathogenesis but also in the development of OA-related symptoms.

Thigh pain and cortical hypertrophies (CH) have been reported in the short term for specific short hip stem designs. The purpose of the study was to investigate 1) the differences in clinical outcome, thigh pain and stem survival for patients with and without CHs and 2) to identify patient and surgery-related factors being associated with the development of CHs. A consecutive series of 233 patients with 246 hips was included in the present retrospective diagnostic cohort study, who had received a total hip arthroplasty (THA) between December 2007 and 2009 with a cementless, curved, short hip stem (Fitmore, Zimmer, Warsaw, IN, USA). Clinical and radiographic follow-up, including the radiographic parameters for hip geometry reconstruction, were prospectively assessed 1, 3, and 6 to 10 years after surgery. Cortical hypertrophies were observed in 56% of the hips after a mean of 7.7 years, compared to 53% after 3.3 years being mostly located in Gruen zone 3 and 5. There was no significant difference for the Harris Hip Score and UCLA score for patients with and without CHs. Only one patient with a mild CH in Gruen zone 5 and extensive heterotopic ossifications around the neck of the stem reported thigh pain. The Kaplan Meier survival rate after 8.6 years was 99.6% (95%-CI; 97.1–99.9%) for stem revision due to aseptic loosening and no association with CHs could be detected. Postoperative increase in hip offset was the only risk factor being associated with the development of CHs in the regression model (ΔHO; OR 1.1 (1.0–1.2); p = 0.001). The percentage of cortical hypertrophies remained almost constant in the mid-term compared to the short-term with the present cementless short hip stem design. The high percentage of cortical hypertrophies seems not be a cause for concern with this specific implant in the mid-term. Diagnostic Level IV