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Adipokines in synovial fluid and serum from OA patients and their relative expression compared with healthy individuals. (a) Leptin levels, (b) adiponectin levels, (c) resistin levels, (d) visfatin levels, (e) chemerin levels, (f) omentin-1 levels, (g) lipocalin-2 levels, (h) vaspin levels, and (i) nesfatin-1 levels. Red lines: synovial fluid concentration in patients with OA; blue lines: serum concentration in patients with OA; black lines: serum concentrations in healthy donors; SF: synovial fluid; HD: healthy donors; ♀: female levels; ♂: male levels.
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Recent studies have shown that overweight and obesity play an important role in the development of osteoarthritis (OA). However, joint overload is not the only risk factor in this disease. For instance, the presence of OA in non-weight-bearing joints such as the hand suggests that metabolic factors may also contribute to its pathogenesis. Recently,...
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... Rheumatoid arthritis (RA) and osteoarthritis (OA) are two most common forms of arthritis in the United States affecting 1.3 million and 30 million people respectively [1][2][3][4]. RA is an autoimmune disease that causes inflammation of the synovial membrane in the joints, leading to joint pain, stiffness, and swelling [5,6]. In contrast, OA is a degenerative joint disease that results from wear and tear of the joints over time, causing pain, stiffness, and loss of mobility [7][8][9]. ...
... At the site of inflammation, chemerin acts as an important chemoattractant for macrophages and dendritic cells [16]. Known chemerin receptors are G-coupled receptors inducing secretion of proinflammatory cytokines like IL (interleukin)-6 and TNF (tumor necrosis factor)-α [17]. An intracellular pathway involving STAT (signal transducer and activator of transcription) 3 signaling has been proposed [18]. ...
... Chemerin is a well-known modulator in the innate immune system and increases the release of proinflammatory cytokines like tumor necrosis factor (TNF)-α or interleukin (IL)-6 [44] via G protein-coupled receptors [17]. Furthermore, chemerin is able to limit bacterial infection [45]. ...
Background: Dysregulation of adipokines is considered a key mechanism of chronic inflammation in metabolic syndrome. Some adipokines affect food intake by crossing the blood/brain barrier. The adipokine chemerin is associated with metabolic syndrome, cardiovascular diseases and immune response. Little is known about chemerin’s presence in cerebrospinal fluid (CSF) and its ability to cross the blood/CSF barrier. Methods: We quantified chemerin levels in paired serum and CSF samples of 390 patients with different neurological diagnoses via enzyme-linked immunosorbent assay (ELISA). Correlation analyses of serum and CSF chemerin levels with anthropometric, serum and CSF routine parameters were performed. Results: Overweight patients exhibited higher chemerin levels in serum and CSF. Chemerin CSF levels were higher in men. Chemerin levels in serum were associated with BMI (body mass index) and CRP (C-reactive protein). Chemerin levels in CSF were associated with age. Neurological diseases affected chemerin levels in CSF. The chemerin CSF/serum ratio was calculated as 96.3 ± 36.8 × 10⁻³ for the first time. Conclusions: Our data present a basis for the development of standard values for chemerin quantities in CSF. CSF chemerin levels are differentially regulated in neurological diseases and affected by BMI and sex. Chemerin is able to cross the blood/CSF barrier under physiological and pathophysiological conditions.
... Additionally, adipokines influence subchondral bone metabolism, promoting sclerosis or increased remodeling, both characteristic of OA, driven by an imbalance between bone formation and resorption [22,23]. They also contribute to synovial inflammation by stimulating the release of pro-inflammatory mediators from synovial cells [24]. (Figure 2). ...
Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability—in particular, between genders. Recent research has increasingly focused on the role of adipokines—especially leptin, adiponectin, and resistin—in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin’s role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease.
... 35 Leptin upregulates the expression of IL-1β and IL-6 via the NF-κB pathway. 36 Leptin activate nitric oxide synthase 2 (NOS2) through the PI3K, and MAPK pathways, thereby promoting cartilage apoptosis and joint degeneration. 37 Leptin induces the production of inducible iNOS in human chondrocytes when acting synergistically with IL-1β in cartilage tissue. ...
Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.
... Adiponectin plays a complex role in OA [57]. Plasma adiponectin levels are associated with clinical and radiographic severity in knee OA, suggesting its potential as a biomarker [58]. ...
Osteoarthritis (OA) is a significant global burden, affecting more than half a billion people across the world. It ischaracterized by degeneration and loss of articular cartilage, synovial inflammation, and subchondral bonesclerosis, leading to pain and functional impairment. After age, obesity is a major modifiable risk factor for OA,and it has recently been identified as a chronic disease by the World Health Organization (WHO). Obesity isassociated with high morbidity and mortality, imposing a significant cost on individuals and society. Obesityincreases the risk of knee OA through increased joint loading, altered body composition, and elevated pro-inflammatory adipokines in the systemic circulation. Moreover, obesity triggers fibrotic processes in differentorgans and tissues, including those involved in OA. Fibrosis in OA refers to the abnormal accumulation of fibroustissue within and around the joints. It can be driven by increased adiposity, low-grade inflammation, oxidativestress, and metabolic alterations. However, the clinical outcomes of fibrosis in OA are unclear. This review focuseson the link between obesity and OA, explores the mechanism of obesity-driven fibrosis, and examines potentialtherapeutic opportunities for targeting fibrotic processes in OA.
... WAT is known to produce a multitude of peptides or proteins, named "adipokines (those produced exclusively by the adipose tissue) or adipocytokines (which can be produced by adipocytes as well as other cell types). Commonly referred to as adipokines, such bioactive molecules can act locally at the cell or tissue level or systemically, therefore in an autocrine or paracrine as well as endocrine manner [89]. They are key players in coordinating immune and metabolic responses correlating nutrient status to body adaptative mechanisms. ...
Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to aging, recent understanding portrays it as a multifactorial degenerative disease of the entire joint. Emerging research highlights metabolic and immune dysregulation in OA pathogenesis, emphasizing the roles of obesity, dyslipidemia, and insulin resistance in altering joint homeostasis. Recent studies have increasingly focused on the complex role of white adipose tissue (WAT) in OA. WAT not only serves metabolic functions but also plays a critical role in systemic inflammation through the release of various adipokines. These adipokines, including leptin and adiponectin, have been implicated in exacerbating cartilage erosion and promoting inflammatory pathways within joint tissues. The overlapping global crises of obesity and metabolic syndrome have significantly impacted joint health. Obesity, now understood to contribute to mechanical joint overload and metabolic dysregulation, heightens the risk of developing OA, particularly in the knee. Metabolic syndrome compounds these risks by inducing chronic inflammation and altering macrophage activity within the joints. The multifaceted effects of obesity and metabolic syndrome extend beyond simple joint loading. These conditions disrupt normal joint function by modifying tissue composition, promoting inflammatory macrophage polarization, and impairing chondrocyte metabolism. These changes contribute to OA progression, highlighting the need for targeted therapeutic strategies that address both the mechanical and biochemical aspects of the disease. Recent advances in understanding the molecular pathways involved in OA suggest potential therapeutic targets. Interventions that modulate macrophage polarization, improve chondrocyte function, or normalize adipokine levels could serve as preventative or disease-modifying therapies. Exploring the role of diet, exercise, and pharmacological interventions in modulating these pathways offers promising avenues for reducing the burden of OA. Furthermore, such methods could prove cost-effective, avoiding the increase in access to healthcare.
... Visfatin, a pro-inflammatory adipokine, plays a role in osteoarthritis pathogenesis by upregulating inflammatory mediators such as TNF-α, IL-6, IL-1β, and various MMPs and ADAMTS enzymes, which are principal agents in cartilage catabolism. Visfatin's levels in serum and synovial fluid are positively correlated with joint damage, biochemical markers of collagen type II and aggrecan degradation, C-reactive protein levels, and the symptomatic manifestations of osteoarthritis [40]. ...
Obesity-related joint pain is a common and debilitating condition that significantly impacts the quality of life, primarily due to the excess weight straining the joints. This results in inflammation and degeneration, which can cause pain, stiffness, and difficulty moving. We aimed to comprehensively review the literature discussing surgical interventions for obesity-related joint pain. We searched across databases (PubMed, Scopus, and Cochrane Library) to identify studies published between 2000 and 2023 that assessed surgical interventions for obesity-related joint pain. This review highlights the complex interplay of mechanical, inflammatory, and metabolic factors contributing to joint pain in obese individuals, highlighting both surgical and non-surgical interventions. Non-surgical interventions include weight loss, exercise, physical therapy, and medications. Surgical interventions include bariatric surgery and joint replacement surgery. Bariatric surgery significantly reduces body weight and improves the quality of life outcomes; however, multiple studies have found no improvement or worsening of joint pain post-surgery. Total joint arthroplasty has demonstrated good improvement in pain and function outcomes based on recent meta-analyses, although risks of complications are higher in obese patients. The treatment choice for obesity-related joint pain depends on the individual patient’s circumstances. Non-surgical interventions are usually the first line of treatment. However, if these interventions are not effective, surgical interventions may be an option.
... В свою чергу вісфатін насьогодні вважають новим прозапальним цитокіном, який має місцеву тканеспецифічну дію і разом з іншими адипокінами за думкою багатьох авторів може сприяти розвитку ОА [14][15][16][17]. В нещодавньому дослідженні було простежене збільшення синтезу вісфатіну в культурі хондроцитів людини при обробці IL-1β [18]. ...
α-Ліпоєва кислота знайшла широке застосування в багатьох терапевтичних напрямках. Поряд з іншими засобами вона є важливою частиною світової боротьбі з діабетом, що наразі доволі широко оприлюднено, в той час як її дія на адипоцитокіновий статус, в т.ч. на рівень вісфатіну, та на клінічні прояви остеоартрозу у жінок, особливо в період менопаузи, потребує подальшого вивчення. Мета дослідження. Оцінити вплив запропонованої схеми терапії з використанням α-ліпоєвої кислоти на показники метаболізму, рівень вісфатіну, а також на клінічні прояви остеоартрозу у пацієнток постменопаузального віку з цукровим діабетом 2 типу та остеоартрозом. Матеріали та методи. Для дослідження було відібрано 44 жінки відповідного віку з цукровим діабетом 2 типу та остеоартрозом, які були розподілені на 2 рівні групи: пацієнтки, що додатково приймали α-ліпоєву кислоту та ті, що її не приймали. Добова доза α-ліпоєвої кислоти становила 600 мг протягом 3 місяців. Визначення рівня вісфатіну у сироватці крові пацієнток проводили імуноферментним методом на аналізаторі «Labline-90» (Австрія). Проведено оцінку показників ліпідного та вуглеводного обміну, клінічних проявів остеоартрозу (шкала ВАШ та WOMAC (Western Ontario and McMaster Universities osteoarthritis Index)). Результати. Виявлено, що пацієнтки, які отримували α-ліпоєву кислоту, мали значно нижчі показники за шкалою ВАШ та WOMAC після лікування, ніж у групі контролю (р<0,05). Після проведення терапії спостерігалося достовірне поліпшення загальних показників глюкозо-інсулінового обміну, але найбільш вірогідні зміни відзначались у жінок, що приймали α-ліпоєву кислоту. Так, виявлено значно нижчі рівні інсуліну крові як порівняно зі значенням до лікування (відповідно 21,5±4,4 та 31,3 ± 3,1 мкМО/мл, р<0,05), так і порівняно до даних контрольної групи після лікування (29,4±1,2 мкМО/мл, р=0,03). У жінок 1 групи відмічено статистично значуще зменшення рівня вісфатіну після 12 тижнів комплексної терапії з додаванням α-ліпоєвої кислоти (від 5,5 ± 1,0 нг/мл до 5,06 ± 1,0 нг/мл (p<0,001)). Висновки. Виявлено позитивний вплив 12-тижневого курсу прийому альфа-ліпоєвої кислоти на параметри глюкозо-інсулінового обміну, ліпідного обміну, рівнів вісфатіну та клінічних показників прояву остеоартрозу у жінок постменопаузального віку з цукровим діабетом 2 типу та остеоартрозом. Обґрунтовано доцільність застосування альфа-ліпоєвої кислоти як додаткового компоненту комплексної терапії жінок постменопаузального віку з цукровим діабетом 2 типу та остеоартрозом.
... It is among the major promoters of cartilage degradation by inhibiting the synthesis of collagen type II and proteoglycans with high molecular weight. Serum and synovial fluid levels of visfatin show a positive correlation with structural damage, markers indicating degradation of collagen type II and aggrecan, CRP levels and OA symptoms [54]. ...
The knee is the joint most frequently involved in osteoarthritis, a common joint disorder in the adult population that is associated with significant chronic joint pain, reduced mobility and quality of life. Recent studies have established an association between obesity and the development of knee osteoarthritis that goes beyond the increased mechanical load on the knees as weight-bearing joints. This link is based on the maintenance of a chronic low-grade inflammation, altered secretion of adipokines by the adipose tissue and development of sarcopenia. Major adipokines involved in the pathogenesis of obesity-related knee osteoarthritis include adiponectin, which appears to have a protective effect, as well as leptin, resistin and visfatin, which are associated with higher pain scores and more severe structural damage. Joint pain in knee osteoarthritis may be both nociceptive and neuropathic and is the result of complex mechanisms driven by nerve growth factor, calcitonin gene-related peptide and pro-inflammatory cytokines. The role of endogenous cannabinoids and gut microbiota in common mechanisms between obesity and knee pain has recently been studied. The aim of the present review is to highlight major pathogenic mechanisms in obesity-related knee osteoarthritis with special attention on pain and to comment on possible therapeutic approaches.
... One of these factors triggering the development and progression of the disease is excessive body weight [14]. Overweight and obesity increase the risk of many diseases, primarily through the metabolic effects of adipose tissue products, i.e., adipokines, whose immunomodulatory activity contributes to the activation of local and systemic inflammatory processes and exacerbation of the catabolic process in the development of OA [15,16]. Many studies have confirmed increased concentrations of adipose tissue products in KOA [17,18]. ...
Osteoarthritis (OA) ranks among the most prevalent inflammatory diseases affecting the musculoskeletal system and is a leading cause of disability globally, impacting approximately 250 million individuals. This study aimed to assess the relationship between the severity of knee osteoarthritis (KOA) and body composition in postmenopausal women using bioimpedance analysis (BIA). The study included 58 postmenopausal females who were candidates for total knee arthroplasty. The control group consisted of 25 postmenopausal individuals with no degenerative knee joint changes. The anthropometric analysis encompassed the body mass index (BMI), mid-arm and mid-thigh circumferences (MAC and MTC), and triceps skinfold thickness (TSF). Functional performance was evaluated using the 30 s sit-to-stand test. During the BIA test, electrical parameters such as membrane potential, electrical resistance, capacitive reactance, impedance, and phase angle were measured. Additionally, body composition parameters, including Total Body Water (TBW), Extracellular Water (ECW), Intracellular Water (ICW), Body Cellular Mass (BCM), Extracellular Mass (ECM), Fat-Free Mass (FFM), and Fat Mass (FM), were examined. The study did not find any statistically significant differences in the electrical parameters between the control (0–1 grade on the K–L scale) and study groups (3–4 grade on the K–L scale). However, statistically significant differences were observed in BMI, fat mass (FM), arm circumference, triceps skinfold thickness, and sit-to-stand test results between the analyzed groups. In conclusion, the association between overweight and obesity with KOA in postmenopausal women appears to be primarily related to the level of adipose tissue and its metabolic activity.
