Curcuma longa and Boswellia serrata Extracts Modulate Different and Complementary Pathways on Human Chondrocytes In Vitro: Deciphering of a Transcriptomic Study.

Objectives: Curcuma longa (CL) and Boswellia serrata (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this in vitro study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes. Methods: BS (10-50 µg/ml) and CL (0.4-2 µg/ml corresponding to 1-5 µM of curcumin) were evaluated separately or in combination on primary chondrocytes isolated from 17 OA patients and cultured in alginate beads. Ten patients were used for RNA-sequencing analysis. Proteomic confirmation was performed either by immunoassays in the culture supernatant or by flow cytometry for cell surface markers after 72 h of treatment. Results: Significant gene expression modifications were already observed after 6 h of treatment at the highest dose of CL (2 µg/ml) while BS was significantly effective only after 24 h of treatment irrespective of the concentration tested. The most over-expressed genes by CL were anti-oxidative, detoxifying, and cytoprotective genes involved in the Nrf2 pathway. Down-regulated genes were principally pro-inflammatory cytokines and chemokines. Inversely, BS anti-oxidant/detoxifying activities were related to the activation of Nrf1 and PPARα pathways. BS anti-inflammatory effects were associated with the increase in GDF15, decrease in cholesterol cell intake and fatty acid metabolism-involved genes, and down-regulation of Toll-like receptors (TLRs) activation. Similar to CL, BS down-regulated ADAMTS1, 5, and MMP3, 13 genes expression. The combination of both CL and BS was significantly more effective than CL or BS alone on many genes such as IL-6, CCL2, ADAMTS1, and 5. Conclusion: BS and CL have anti-oxidative, anti-inflammatory, and anti-catabolic activities, suggesting a protective effect of these extracts on cartilage. Even if they share some mechanism of action, the two extracts act mainly on distinct pathways, and with different time courses, justifying their association to treat osteoarthritis.

Patients' Expectations Impact Their Satisfaction following Total Hip or Knee Arthroplasty.

INTRODUCTION: The objective of this study was to assess the number and magnitude of preoperative expectations and to correlate them with the degree of satisfaction expressed one year after Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA), in patients with severe and painful osteoarthritis (OA). MATERIALS AND METHODS: Preoperative expectations (within 20 days prior to surgery) and postoperative satisfaction (one year after the intervention) were measured using the previously validated French version of the Hospital for Special Surgery Hip or Knee Replacement Expectations Survey. Postoperative satisfaction was measured using a specific scale, following the same methodology as that used for the assessment of expectations. Prediction of the satisfaction of the patients was performed using multivariate linear regression modelling. RESULTS: A total of 138 patients (80 THA and 58 TKA) completed the two parts of the study. The expectations score (mean ± SD) (range 0-100) was 72.58 ± 12.63 before THA and 69.10 ± 13.72 before TKA (p = 0.13). The number of expectations expressed was 14.34 ± 1.32 (out of a potential maximum of 18) before THA and 14.70 ± 2.29 (out of a potential maximum of 19) before TKA. After 1 year, THA generated a significantly higher degree of satisfaction compared to TKA (69.70 ± 14.46 v 60.44 ± 17.54, p<0.001) (range 0-100). The pre-operative expectations score was the single best positive predictor of the post-surgery satisfaction assessment both for TKA and THA. CONCLUSION: Patients undergoing total joint arthroplasty for end-stage OA have a high level of expectations, before both THA and TKA. While both types of interventions significantly improve essential and non-essential activities, the rate of satisfaction is significantly greater post THA. Preoperative expectations are a major contributor to the final degree of satisfaction, one year after surgery. These results re-emphasize the need for an optimal preoperative interaction between health care providers and patients, to allow patients a chance to foresee a reasonable outcome after TJA.

Development and validation of the French version of a tool assessing patient's expectations in lower limb osteoarthritis.

OBJECTIVE: The Hospital for Special Surgery (HSS) Hip Replacement Expectations Survey and Knee Replacement Expectations Survey are validated tools developed to measure patients' preoperative expectations for hip and knee arthroplasty. These instruments have possible uses in both daily practice and research. Our objective was to assess the test-retest reliability and the construct validity of the French version of the surveys. METHODS: Patients scheduled for total hip (n = 82) or knee replacement (n = 61) aged 38-90 years were included. All completed the HSS Hip or Knee Replacement Expectations Survey and the Expectation WOMAC to determine concurrent validity. The test-retest reliability was assessed using the intraclass coefficient correlation (ICC), the Bland and Altman Method and the coefficient of variation; the internal consistency was assessed by the Cronbach α coefficient. The construct validity was investigated using the Pearson correlation coefficient and floor and ceiling effects by percentage frequency of lowest or highest possible score achieved by respondents. RESULTS: 143 patients scheduled for hip or knee arthroplasty were included. The reliability was excellent between the test and the rested total score, with an ICC of 0.902 (0.853-0.936) and CV of 4.06% for the French Hip Replacement Expectations Survey and 0.865 (0.786-0.917) and CV of 7.7% for the French Knee Replacement Expectations Survey, without bias. The Cronbach α coefficient was 0.72 for hip Survey and 0.82 for knee Survey showing a good internal consistency. Pearson correlation coefficients of 0.45 and 0.48 between Expectations WOMAC and HSS, respectively for hip Survey and knee Survey, were observed but with systematic bias. The lowest possible score was not reported by any patient and only three patients (3.66%) scheduled for hip arthroplasty reported the highest possible score. CONCLUSIONS: The French version of the HSS Hip or Knee Replacement Expectations Survey is a reliable and valid questionnaire and compares favourably with the original English version. Therefore, this new version may help French-speaking clinicians to evaluate expectations before lower limb arthroplasty.

Regulation of subchondral bone osteoblast metabolism by cyclic compression.

OBJECTIVE: Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure applied to the articulation was responsible for these metabolic changes. This study was undertaken to evaluate the effects of cyclic compression on osteoblasts from OA subchondral bone. METHODS: Osteoblasts were isolated from sclerotic and nonsclerotic areas of human OA subchondral bone. After 28 days, the osteoblasts were surrounded by an abundant extracellular matrix and formed a resistant membrane, which was submitted to cyclic compression (1 MPa at 1 Hz) for 4 hours. Gene expression was evaluated by reverse transcription-polymerase chain reaction. Protein production in culture supernatants was quantified by enzyme-linked immunosorbent assay or visualized by immunohistochemistry. RESULTS: Compression increased the expression of genes coding for interleukin-6 (IL-6), cyclooxygenase 2, RANKL, fibroblast growth factor 2, IL-8, matrix metalloproteinase 3 (MMP-3), MMP-9, and MMP-13 but reduced the expression of osteoprotegerin in osteoblasts in both sclerotic and nonsclerotic areas. Colα1(I) and MMP-2 were not significantly affected by mechanical stimuli. Nonsclerotic osteoblasts were significantly more sensitive to compression than sclerotic ones, but after compression, differences in messenger RNA levels between nonsclerotic and sclerotic osteoblasts were largely reduced or even abolished. Under basal conditions, sclerotic osteoblasts expressed similar levels of α5, αv, ß1, and ß3 integrins and CD44 as nonsclerotic osteoblasts but 30% less connexin 43, an important mechanoreceptor. CONCLUSION: Genes involved in subchondral bone sclerosis are mechanosensitive. After compression, nonsclerotic and sclerotic osteoblasts expressed a similar phenotype, suggesting that compression could be responsible for the phenotype changes in OA subchondral osteoblasts.