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Pro-inflammatory mediators IL-1β and TNFα secreted by fibroblast-like synoviocytes bind to receptors on chondrocytes to promote synthesis of matrix metalloproteinases which then break down cartilage leading to progression of osteoarthritis, which is characterized by the cardinal features of narrowed joint space, osteophytosis, subchondral sclerosis and cyst formation.
Source publication
Osteoarthritis (OA) is a global health issue with myriad pathophysiological factors and is one of the most common causes of chronic disability in adults due to pain and altered joint function. The end stage of OA develops from a destructive inflammatory cycle, driven by the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis facto...
Contexts in source publication
Context 1
... OA patients. 19 Through complex mechanisms, these cytokines exert their anti-inflammatory effects following a reduction in the production of IL-1β, TNFα, MMPs and other inflammatory mediators. 19 Amongst all, there is compelling evidence that IL-1β and TNFα are the most important pro-inflammatory mediators in the development and progression of OA (Fig. 1). 20,21 IL-6, a pro-inflammatory cytokine enhanced by TNFα and IL-1β, has been known to inhibit type II collagen synthesis. 22 A longitudinal study on women with knee OA through 15 years of follow-up reveals that higher levels of serum IL-6 is associated with an increased chance of diagnosis of OA. 23 While IL-6 has been proposed as a ...
Context 2
... OA patients. 19 Through complex mechanisms, these cytokines exert their anti-inflammatory effects following a reduction in the production of IL-1β, TNFα, MMPs and other inflammatory mediators. 19 Amongst all, there is compelling evidence that IL-1β and TNFα are the most important pro-inflammatory mediators in the development and progression of OA (Fig. 1). 20,21 IL-6, a pro-inflammatory cytokine enhanced by TNFα and IL-1β, has been known to inhibit type II collagen synthesis. 22 A longitudinal study on women with knee OA through 15 years of follow-up reveals that higher levels of serum IL-6 is associated with an increased chance of diagnosis of OA. 23 While IL-6 has been proposed as a ...
Citations
... Orthobiologic treatments have gained attention as a more sustainable approach to tackling the increasing problem of OA. [16] The introduction of bone-marrow aspirate concentrate (BMAC) has resulted in greater ease of use and better acceptance by clinicians and patients [17]. Various techniques for concentrating bone-marrow aspirate to form BMAC have been proposed. ...
Hip osteoarthritis (OA) is one of the leading causes of disability and morbidity worldwide. It is estimated to affect 9.2% individuals globally with age over 45 years. Conventional treatment modalities have limitations and side-effects. To overcome these limitations, over the last decade, there has been an increased interest in the use of orthobiologics derived from autologous sources including platelet-rich plasma (PRP), bone-marrow aspirate concentrate (BMAC) and adipose tissue derived formulations. This review qualitatively presents the in-vitro, pre-clinical, clinical and on-going clinical studies exploring the safety and efficacy of BMAC for management of hip OA.
The electronic database search was done through PubMed, Embase, Web of Science, Scopus, ProQuest and Google Scholar till February 2024. The search terms used were “osteoarthritis” OR “hip osteoarthritis” OR “orthobiologics” OR “efficacy or use of orthobiologic treatment” OR “bone-marrow concentrate” OR “bone-marrow aspirate concentrate”, AND “BMAC”. The inclusion criteria were clinical studies of any level of evidence written in the English language, published till February 2024, evaluating the safety and efficacy of intra-articular administration of BMAC for the management of hip OA.
A total of 5 studies were included in this review for qualitative data synthesis. The total number of patients who participated in the study was 182, ranging from 4 to 112 in a single study. No adverse events were reported throughout the duration of the study. In addition, intra-articular administration of BMAC led to reduced pain, and improved function and overall quality of life (QoL).
The results from this review demonstrated that administration of BMAC is safe and potentially efficacious in terms of reducing pain, improving function and overall QoL of patients with hip OA in short- and mid-term average follow-up based on the included studies. Nonetheless, more adequately powered, multi-center, prospective, double-blind, non-randomized and randomized controlled trials with long-term follow-up are warranted to establish long-term safety and efficacy of BMAC for management of hip OA and justify its routine clinical use.
... APS contains components that block the action of these inflammatory cytokines [11]. APS reportedly reduces knee OA pain and prevents OA progression [12]. It is effective in patients with synovitis-derived intra-articular hydrops and is recommended for patients with persistent intra-articular hydrops. ...
Knee osteoarthritis (OA) is a multifaceted metabolic disorder influenced by biomechanical, inflammatory, and immune system factors. Although autologous protein solution (APS) and extracorporeal shock wave therapy (ESWT) have shown promise for treating mild-to-moderate knee OA, their efficacy for severe cases remains limited when administered individually. Thus, we examined the combination effects of APS and ESWT for severe knee OA. Twenty-four cases (33 knees) of Kellgren–Lawrence grade 4 knee OA with bone marrow lesions and synovitis detected via magnetic resonance imaging from December 2019 to November 2022 were included. All patients underwent an ESWT session before the APS injection. The study included 20 knees in the APS + ESWT group, which underwent an average of 4.5 ESWT sessions, and 13 in the APS-alone group. We evaluated both groups’ Knee Injury and Osteoarthritis Outcome Scores (KOOSs) before the APS injection at 3 and 6 months. Additionally, we compared the mean KOOS changes between the APS + ESWT and APS-alone groups at 3 months (Pre-3M) and from 3 to 6 months (3–6M). Pre-3M showed no significant difference in the KOOSs between the two groups; however, there was a significant change in 3–6M (p < 0.05). Combining APS therapy with ESWT in severe knee OA was more effective and durable than APS alone.
... Primary OA, more prevalent than secondary OA, is associated with a detrimental inflammatory cycle, led by pro-inflammatory cytokines, including IL-1β and tumor necrosis factor-alpha (TNF-α) [13,14]. Proinflammatory cytokines play a vital role in cartilage matrix degradation via increased production of matrix metalloproteinases. ...
... Proinflammatory cytokines play a vital role in cartilage matrix degradation via increased production of matrix metalloproteinases. This results in the initiation of the inflammatory response, which triggers a positive feedback loop involving inflammatory cytokines-induced tissue damage, leading to further production of inflammatory cytokines [13,14]. This vicious cycle results in continued degradation of cartilage, causing advanced OA [13,14]. ...
... This results in the initiation of the inflammatory response, which triggers a positive feedback loop involving inflammatory cytokines-induced tissue damage, leading to further production of inflammatory cytokines [13,14]. This vicious cycle results in continued degradation of cartilage, causing advanced OA [13,14]. APS is formulated to manage OA by targeting the inflammatory pathways mediated by IL-1β and TNF-α. ...
Knees are the most regularly affected weight-bearing joints in osteoarthritis (OA), impacting millions of individuals across the globe. The incidence of knee OA will further rise with increasing rates of obesity and lifespan, resulting in a significant increase in the worldwide socioeconomic burden. Conventional therapies used to manage the symptoms associated with knee OA have limitations. Lately, there has been an increased interest in the use of autologous peripheral blood-derived orthobiologics (APBO), including autologous protein solution (APS), for the management of knee OA. Here, the primary objective is to summarize the outcomes of clinical studies involving APS for the treatment of knee OA. Several databases (Embase, Scopus, PubMed, and Web of Science) were searched using terms for the intervention “APS” and treatment “knee OA” for articles published in English until January 21, 2024. All clinical studies using APS as an intervention for the treatment of knee OA were included. Studies not utilizing APS alone or not aiming at the management of knee OA were excluded. Six clinical studies that met our predefined search terms and inclusion and exclusion criteria were included in this study. The results demonstrated that the intra-articular administration of APS is safe and efficacious in reducing pain and/or improving function in patients suffering from knee OA. However, more multicenter, randomized controlled trials involving active comparators, with adequate power and long-term follow-up along with post-market real-world studies in clinical practice are required to further assess the efficacy of APS and justify its regular clinical use for the management of knee OA.
... In this context, interleukin-1β and tumor necrosis factor-α are secreted by synovial fibroblasts and chondrocytes in individuals with OA. These promote the synthesis of protein hydrolases, which degrade the joint extracellular matrix; this, in turn, drives disease progression, worsens disease-related synovial inflammation, and induces cartilage degeneration and the formation of subchondral bone lesions (32)(33)(34). Dietary probiotic supplementation promotes balance in the intestinal flora and reduces the inflammatory response, thereby reducing the risk of OA. Probiotics are effective in combating inflammation caused by interleukin-1β and tumor necrosis factor-α. ...
Objective
Osteoarthritis (OA) is associated with cardiovascular disease and represents a persistent economic and physical burden on patients in the United States. This study evaluated the mediating effect of dietary live microbe intake on the association between cardiovascular health [based on Life's Essential 8 (LE8) scores] and osteoarthritis (OA) in adults.
Methods
This cross-sectional study included data from the National Health and Nutrition Examination Survey, 1999–2019 (from patients aged ≥20 years). LE8 scores (0–100) were measured according to the American Heart Association definition and categorized as low (0–49), moderate (50–79), or high (80–100). OA disease status was assessed using self-reported data from patients. The relationships were evaluated using multivariate logistic and restricted cubic spline models. Mediation analysis was used to evaluate the mediating effect of dietary live microbe intake on the association between LE8 and OA risk.
Results
The study included 23,213 participants aged ≥20 years. After adjusting for latent confounders, higher LE8 scores were found to be associated with a lower incidence of OA. The odds ratios (with 95% confidence intervals) for low, moderate, and high OA risk were 0.81 (0.69, 0.96) and 0.55 (0.44, 0.69), respectively; a non-linear dose-response relationship was observed (P-nonlinear = 0.012). Health behavior and health factor scores showed a similar pattern of correlation with OA risk. Low live microbe intake mediated the association between LE8, health behavior, and health factor scores with OA risk and did not appear to reduce OA risk.
Conclusion
Our findings suggest that although higher LE8 scores reduce the risk of developing OA, low live microbe intake may reduce the protective effect of higher scores. It is, therefore, essential to emphasize adherence to a lifestyle that confers high LE8 scores. Individuals should also be advised to reduce the intake of foods with low live microbe content.
... Reducing proinflammatory cytokine production (e.g., IL-1β and TNF-α are some of the most important therapeutic aims in OA [5], as these inflammatory mediators play important roles in the destructive changes in cartilage and modification to subchondral bone structural changes in OA [8,9]. The secretion of IL-1β and TNF-α from OA synovial fibroblasts and chondrocytes promote the synthesis of proteolytic enzymes that degrade joint extracellular matrices and thus drive OA, worsening the disease-related synovial inflammation, cartilage degeneration, and subchondral bone lesions [9][10][11]. In experimental OA, inhibiting or reducing pro-inflammatory expression suppresses joint degradation, highlighting the importance of such strategies for OA treatment [12,13]. ...
... Proinflammatory cytokines have an important role in OA joint destruction [8,37], promoting damage in joint extracellular matrices and stimulating the progression of OA [9,10]. High IL-1β and TNF-α levels upregulate proteolytic enzymes, such as MMPs and ADAMTS family, which degrade the extracellular matrix [9,11]. ...
Osteoarthritis (OA) is a painful, progressive chronic inflammatory disease marked by cartilage destruction. Certain synovial inflammatory cytokines, such as IL-1β and TNF-α, promote OA inflammation and pain. Lactobacillus spp. is a well-known probiotic with anti-inflammatory, analgesic, antioxidant, and antiosteoporotic properties. This study evaluated the therapeutic effects of a live L. plantarum strain (GKD7) in the anterior cruciate ligament transection (ACLT)-induced OA rat model. The results show that oral administration of live L. plantarum GKD7 improved weight-bearing asymmetry after ACLT surgery. Moreover, micro-computed tomography images and histopathological analysis show that oral live L. plantarum GKD7 improved subchondral bone architecture, protected articular cartilage against ACLT-induced damage, and reduced synovial inflammation. L. plantarum GKD7 also reduced IL-1β and TNF-α production in OA cartilage and synovium. Thus, orally administered live L. plantarum GKD7 appears to effectively slow the progression of OA.
Orthobiologics are rapidly growing in use given their potential to augment healing for multiple musculoskeletal conditions. Orthobiologics consist of a variety of treatments including platelet-rich plasma and stem cells that provide conceptual appeal in providing local delivery of growth factors and inflammation modulation. The lack of standardization in nomenclature and applications within the literature has led to a paucity of high-quality evidence to support their frequent use. The purpose of this review was to describe the current landscape of orthobiologics and the most recent evidence regarding their use.
