ObjectiveProteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis.MethodsOA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain.ResultsOsteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone.ConclusionsThis study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes.

No abstract

Background:As of the 25th of January 2021, more than 150 thousand deaths as consequence of COVID-19 have been reported in Mexico [1]. Advanced age, male gender and comorbidities have been described as risk factors for severe disease and mortality in general population [2]. COVID-19 mortality in Mexican patients with rheumatic and musculoskeletal diseases (RMDs) is unknown.Objectives:To describe characteristics of Mexican patients with RMDs and COVID-19, and to analyse factors associated with mortality.Methods:The Global Rheumatology Alliance COVID-19 (GRA) physician reported registry, is an international effort to collect information on COVID19 in adult patients with RMDs. GRA is an observational registry. The first patient from Mexico was registered on April 17, 2020. All Mexican patients registered in GRA until October 30, 2020 were included in this analysis. The association of mortality with demographic and clinical variables was estimated using logistic regression analysis.Results:A total of 323 patients were registered, with a median age of 52 (IQR 41-61) years old, 166 (51.4%) patients lived in Mexico City. The most frequent RMDs were rheumatoid arthritis, 149 (46.1%) and systemic lupus erythematosus, 24 (19.8%). Over a third of patients with RMDs and COVID-19 (119 (36.8%)) were hospitalized, and 43 (13.3%) died. Table 1 shows clinical and demographic characteristics. In the univariable analysis, the absence of comorbidities was a protective factor, OR 0.3 (95% CI 0.1-0.6). Factors associated with mortality at COVID-19 diagnosis were age over 65 years old, having type 2 diabetes, chronic renal insufficiency, treatment at COVID-19 diagnosis with corticosteroids or with CD20 inhibitors. In the multivariable adjusted analysis, these factors remained independently associated with mortality. No associations with other treatments or comorbidities at COVID-19 diagnosis were found.Conclusion:Mexican patients with RMDs and COVID-19 in the GRA physician reported registry had a mortality of 13.3%. Factors associated with mortality were those described in the general population, such as older age and being on corticosteroids and CD20 inhibitors treatment at COVID-19 diagnosis.References:[1]WHO. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. (accessed 26 January, 2021).[2]Zhou F, et al. Lancet 2020;395(10229):1054-62.Table 1.Clinical and demographic characteristics of patients with rheumatic diseases and COVID-19 in Mexico and mortality.Characteristics at COVID-19 diagnosisTotalN=323Death43 (13.3)Survivors280 (86.7)UnivariableOR (95% CI)MultivariableOR (95% CI)Women, n(%)268 (82.9)33 (76.7)235 (83.9)0.6 (0.3-1.4)0.5 (0.2-1.3)Age >65 years old, n(%)62 (19.2)18 (41.9)44 (15.7)3.9 (1.9-7.7)3.9 (1.9-8.3)RMDs* n(%)-Rheumatoid arthritis149 (46.1)23 (53.5)126 (45.0)1.6 (0.7-3.7)-Systemic Lupus Erythemathosus64 (19.8)10 (23.3)54 (19.3)1.6 (0.6-4.3)-Spondyloarthritis (axial and others)33 (10.2)2 (4.7)31 (11.1)0.1 (0.1-2.8)-Others77 (23.8)8 (18.6)69 (24.6)1-Moderate/High disease activity1, n(%)57 (18.6)7 (17.9)50 (18.7)1.0 (0.4-2.5)-None comorbidities, n(%)136 (42.1)8 (18.6)128 (45.7)0.3 (0.1-0.6)-Hypertension*, n(%)88 (27.2)12 (27.9)76 (27.1)1.0 (0.5-2.1)-Type 2 Diabetes*, n(%)49 (15.2)13 (30.2)36 (12.9)2.9 (1.4-6.1)2.4 (1.1-5.4)Obesity*, n(%)21 (6.5)3 (6.9)18 (6.4)1.1 (0.3-3.9)-Chronic obstructive pulmonary disease*, n(%)15 (4.6)1 (2.3)14 (5.0)0.5 (0.1-3.5)-Chronic renal insufficiency*, n(%)17 (5.2)6 (13.9)11 (3.9)3.9 (1.4-11.4)3.4 (1.1-10.4)Cardiovascular diseases*, n(%)14 (4.3)2 (4.7)12 (4.3)1.1 (0.2-5.0)-Corticosteroids*, n(%)171 (52.9)30 (69.7)141 (50.3)2.3 (1.1-4.5)3.0 (1.4-6.5)CsDMARD*, n(%)247 (76.5)33 (16.3)214 (76.4)1.0 (0.5- 2.2)-CD20 inhibitor*, n(%)21 (6.5)7 (16.3)14 (5.0)3.7 (1.4-9.9)4.9 (1.7-14.5)*Overlapped, 1 307 patients.Disclosure of Interests:None declared

Exercise is recommended as a non-pharmacological therapy for osteoarthritis (OA). Various exercise regimes, with differing intensities and duration, have been used in a range of OA rodent models. These studies show gentle or moderate exercise reduces the severity of OA parameters while high intensity load bearing exercise is detrimental. However, these studies were largely conducted in rats or in mouse models induced by severe injury, age or obesity, whilst destabilization of the medial meniscus (DMM) in mice has become a widely accepted model due to its lower variability, moderate progression and timescale. The present study was undertaken to provide insight into the effect of moderate exercise on early joint pathology in the DMM mouse model. Exercise was induced a week after induction by forced wheel walking for three or 7 weeks. Joints were analyzed by microcomputed tomography and histology. Assessment of skeletal parameters revealed that exercise offered protection against cartilage damage after 7 weeks of exercise, and a temporary protection against osteosclerosis was displayed after 3 weeks of exercise. Furthermore, exercise modified the metaphyseal trabecular microarchitecture of the osteoarthritic leg in both time points examined. Collectively, our findings corroborate previous studies showing that exercise has an important effect on bone in OA, which subsequently, at 8 weeks post-induction, translates into less cartilage damage. Thus, providing an exercise protocol in a surgical mouse model of OA, which can be used in the future to further dissect the mechanisms by which moderate exercise ameliorates OA.

Background:COVID-19 outcomes in Mexican patients with rheumatic diseases (RDs) in comparison to general population patients are unknown.Objectives:To compare mortality and hospitalization of COVID-19 patients with RDs and those without.Methods:We included for this study all the Mexican patients with RDs and COVID-19 registered from April 17th to October 30th, 2020 in the COVID-19 Global Rheumatology Alliance registry. We compare clinical and demographic characteristics of patients with RDs and COVID-19 to patients with COVID-19 that were selected randomly from the Mexican Epidemiology database (1:3). A logistic regression analysis was performed to adjust for confusion variables.Results:We included 322 patients with COVID-19 and RDs and 969 controls without RDs. Table 1 shows the demographic characteristics and comorbidities of both groups. Bivariate analysis showed that patients with RDs had higher mortality, were older, and were more frequently hospitalized. Comorbidities, such as diabetes, hypertension, cardiovascular and renal diseases were also more frequent in patients with RDs. In the multivariate analysis, having a RD was no longer associated with mortality (Figure 1).Figure 1.Multivariate analysis of mortalityConclusion:Patients with RDs had higher comorbidities, hospitalizations, and mortality than the general population in the bivariate analysis. However, adjusted multivariate analysis showed that the odds for mortality were not increased because of having a RD. These findings suggest that the increased mortality of Mexican patients with RDs may be explained by the higher frequency of comorbidities in this population.Table 1.Comparison of patients with COVID-19 with and without RDsCOVID-19 patients without RDsCOVID-19 patients with RDsp-valueN969323Age (mean (SD))42.6 (17.4)51.2 (13.9)<0.001Sex = Male (%)455 (47.0)55 (17.0)<0.001Deceased = Yes (%)55 (5.7)43 (13.3)<0.001Hospitalization = Hospitalized (%)164 (16.9)152 (47.1)<0.001Intubation = Yes (%)27 (2.8)32 (11.8)<0.001COPD_Asthma = Yes (%)37 (3.8)15 (4.6)0.522Diabetes = Yes (%)114 (11.8)49 (15.2)0.116Obesity = Yes (%)128 (13.3)21 (6.5)0.001Hypertension = Yes (%)152 (15.8)88 (27.2)<0.001Cardiovascular disease = Yes (%)19 (2.0)14 (4.3)0.02CRF = Yes (%)22 (2.3)17 (5.3)0.007Pregnancy = Yes (%)5 (0.5)2 (0.6)0.827Smoker = Yes (%)86 (8.9)10 (3.1)0.001Abbreviations: RDs, rheumatic diseases; COPD, chronic obstructive pulmonary disease; CRF, chronic renal failure.Disclosure of Interests:None declared