Estrogens,cartilage, and osteoarthritis

A role for estrogens in osteoarthritis is consistent with the larger increases in women than in men in the incidence and prevalence of hip, knee, and finger osteoarthritis after 50 years of age. Furthermore, hormone replacement therapy for the menopause seems to be associated with a decrease in the prevalence of symptoms and radiological alterations related to hip and knee osteoarthritis. The two estrogen receptors alpha and beta (ERalpha and Erbeta) have been identified in normal and osteoarthritic cartilage, indicating that cartilage can respond to estrogens. Finally, in vivo experiments in animals and in vitro studies have shed light on the mechanisms by which estrogens may influence chondrocyte metabolism.     

Estrogens,osteoarthritis and inflammation

Estrogens participate in several biological processes through different molecular mechanisms. Their final actions consist of a combination of both direct and indirect effects on different organ and tissues. Estrogen may have pro- and anti-inflammatory properties depending on the situation and the involved tissue. In general, acute loss of estrogens increases the levels of reactive oxygen species and activates nuclear factor-κB and pro-inflammatory cytokine production, indicating their predominant anti-inflammatory properties. Furthermore, pro-inflammatory cytokine expression has been shown to be attenuated by estrogen replacement. Osteoarthritis and cardiovascular disease are two of the more prevalent diseases once menopause is established, which has suggested the link between estrogens and both processes. In addition, deletion of estrogen receptors in female mice results in cartilage damage, osteophytosis and changes in the subchondral bone of the joints suggesting that estrogens have a protective role on the maintenance of joint homeostasis. Furthermore, in spite of the negative effect of estrogen replacement reported in 2002 by the Women's Health Initiative study, several works published afterwards have explored the potential protective effect of estrogen supplementation in animal models and have postulated that these actions may justify a beneficial role of estrogens in different diseases where inflammation is the major feature. In this review, we will analyze the effects of estrogens on certain pathological situations such as osteoarthritis, some autoimmune diseases and coronary heart disease, especially in postmenopausal women.     

Epigenetics,sirtuins and osteoarthritis

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in different pathologies, including inflammatory diseases and age-related diseases such as osteoarthritis (OA). In this review, we focus on the chromatin-modifying enzymes in arthritic pathologies, and more particularly on Sirtuins. We also review the role of Sirt1 in OA, which has been highlighted in recent publications, and examine the possible protective role Sirt1 could play in this disease. Moreover, we discuss the possible therapeutic target of such a protein, reviewing the potential inhibitors/activators of this enzyme and their properties.     

Sports, joint injury, and posttraumatic osteoarthritis

Participation in sports increases the risk of joint injuries that can lead to posttraumatic osteoarthritis, a clinical syndrome caused by trauma-initiated joint degeneration that results in permanent and often progressive joint pain and dysfunction. Minimizing the risk of joint injuries and helping people with osteoarthritis participate in regular physical activity, including some sports, requires understanding of the relationships between joint use, joint injury, and joint degeneration. Lifelong participation in sports that cause minimal joint impact and torsional loading by individuals with normal joints and neuromuscular function does not increase the risik of posttraumatic osteoarthritis. In contrast, participation in sports that subject joints to high levels of impact and torsional loading increases the risk of joint injury and subsequent joint degeneration. Immediate diagnosis and appropriate treatment and rehabilitation following joint injuries decrease the risk of subsequent injuries and posttraumatic osteoarthritis. Individuals with abnormaljoint anatomy or alignment, previous significant joint injury, osteoarthritis, joint surgery, joint instability, disturbances of joint or muscle innervation or inadequate muscle strength have increased risk of joint damage during participation in athletics. These individuals can benefit from regular exercise, including selected sports, but they should have an evaluation of their joint structure and function, muscle strength, and neuromuscular function before participating in vigorous physical activity.     

Gait patterns,symptoms, and function in patients with isolated tibiofemoral osteoarthritis and combined tibiofemoral and patellofemoral osteoarthritis

The purpose of this study was to compare hip and knee biomechanics during walking in individuals with isolated tibiofemoral osteoarthritis (TFOA), combined TFOA and patellofemoral osteoarthritis (PFOA), and those without knee osteoarthritis (OA), and to compare patient‐reported symptoms and function in individuals with isolated TFOA and those with combined TFOA and PFOA. Participants with and without knee OA were assessed and categorized into (i) no OA, (ii) isolated TFOA, and (iii) combined TFOA and PFOA, based on Kellgren and Lawrence diagnostic criteria. Quantitative motion analyses were conducted during walking, and hip and knee kinematics, and external moments were calculated. Peak values in the sagittal and frontal planes during stance phase were computed. Patient‐reported symptoms and function data were obtained using the Western Ontario McMaster Universities Arthritis Index. Multivariate analyses of variance were conducted to compare between‐group differences in gait and patient‐reported symptoms and function data. The results showed no statistically significant differences in hip and knee kinematics and external moments between the three groups. Relative to those with isolated TFOA, individuals with combined TFOA and PFOA had greater pain (mean difference [95%CI]: 1.5 [0.05–3.1]), stiffness (0.8 [0.02–1.5]), and poorer function (5.4 [0.2–10.7]). In conclusion, the combined TFOA and PFOA radiographic disease pattern is associated with worse pain and function compared to the isolated TFOA disease pattern. The results of the present study provide no indications that treatments designed to change walking biomechanics should differ between individuals with isolated TFOA and those with combined TFOA and PFOA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1666–1672, 2018.

     

CALM1基因及钙调素与骨关节炎

骨关节炎(OA)以进行性关节软骨丢失、骨赘形成等退行性变为主要特征。多功能受体蛋白钙调素(CaM)在真核细胞Ca~(2 )信号转导通路中发挥重要作用。关节软骨内Ca~(2 )-CaM信号对软骨细胞的分化形成具有重要作用;给予关节软骨适当的压力负荷刺激能诱导软骨基质合成增加,而这一反应似乎必须依赖于Ca~(2 )-CaM信号通路。软骨细胞内Ca~(2 )-CaM信号通路一旦发生异常,可能会引起软骨细胞分化形成、软骨细胞粘附能力、关节软骨修复及对压力负荷刺激的反应性等方面的异常,进而促进OA的发生、发展。近期研究表明,编码CaM的CaM基因之一CALM1的单核苷酸多态性与OA易感性相关,这一发现从基因和分子转录水平提示CaM及Ca~(2 )-CaM信号通路异常在OA发病机制中的作用。     

Pain,function, and radiographic disease in trapeziometacarpal osteoarthritis

IntroductionTrapeziometacarpal joint osteoarthritis (OA) produces significant functional impairment due to pain and loss of strength in both power and precision grips, but few studies have related radiographic scores to functional and pain-based measures.PurposeTo investigate the association between markers of radiographic disease and outcomes for symptomatic and functional disease.Study DesignThis study in an exploratory analysis of baseline data from the first 100 participants in a clinical trial evaluating the efficacy of combined conservative therapies for base of thumb OA (COMBO).MethodsFunctional Index for Hand Osteoarthritis (FIHOA) scores and Visual Analogue Scale (VAS) scores for pain were recorded for the index hand. Bilateral isometric grip and tip-pinch strength measurements were taken, as well as posteroanterior and Eaton stress-view hand radiographs. Generalized estimating equations (GEEs), univariate, and multivariate analyses were used according to whether the data were bilateral or unilateral.ResultsA total of 79 females and 21 males were included, with a median Kellgren-Lawrence (KL) grade of 3 in the index hand. Higher KL and Eaton grades were associated with lower grip strength in the GEE analysis (B-coefficients of -1.25 and -1.16, and P-values of .002 and .010, respectively). Higher KL grade was also associated with poorer function and higher pain levels in the multivariable analysis (B-coefficients of 1.029 and 3.681, and P-values of .021 and .047, respectively). Lower radial subluxation ratios were associated with lower grip strength in the GEE analysis, and higher pain scores in the multivariable analysis (B-coefficients of 2.06 and -42.1, and P-values of .006 and .031, respectively). Greater pain scores were also associated with poorer function (B-coefficient 0.082, P-value .001).ConclusionMore advanced radiographic trapeziometacarpal OA severity is associated with lower grip strength and poorer self-reported functional outcomes. Lower subluxation ratios were associated with higher pain scores and lower grip strength.     

Meniscus pathology, osteoarthritis and the treatment controversy

The menisci are internal structures that are of central importance for a healthy knee joint; they have a key role in the structural progression of knee osteoarthritis (OA), and the risk of the disease dramatically increases if they are damaged by injury or degenerative processes. Meniscus damage might be considered a signifying feature of incipient OA in middle-aged and elderly people. As approximately every third knee of people in these groups has a damaged meniscus, tears are common incidental findings of knee MRI. However, as most tears do not cause symptoms, careful clinical evaluation is required to determine if a damaged meniscus is likely to directly impact a patient's symptoms. Conservative management of patients with knee pain and a degenerative meniscal tear should be considered as a first-line therapy before surgical treatment is contemplated. Patients with mechanical interference of joint movements, such as painful catching or locking, might need surgical treatment with meniscal repair if possible. In a subset of patients, meniscal resection might relieve pain and other symptoms that potentially originate directly from the torn meniscus. However, the possibility of an increased risk of OA if functional meniscal tissue is removed cannot be overlooked.