Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

Sun, Aijuan; Udduttula, Anjaneyulu; Li, Jian; Liu, Yanzhi; Ren, Pei‐Gen; Zhang, Peng

doi:10.1016/j.jot.2020.07.004

Cited by 40 publications

(25 citation statements)

References 177 publications

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“…Epidemiology study has shown that hand OA was seen in ∼60% of North American and European adults ≥65 years of age—far greater than the ∼33% found in the knee and ∼5% in the hip ( Plotz et al, 2021 ). Increasing evidence suggests that there are multiple subtypes of OA that reflect a complex and multifactorial nature, in which obesity-induced OA has been proposed as a new phenotype of OA that displays a unique characteristic ( Sun et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Adipokine Signaling Pathways in Osteoarthritis

Zhang

Lin

Yan

et al. 2022

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is a debilitating joint disease that affects millions of individuals. The pathogenesis of OA has not been fully elucidated. Obesity is a well-recognized risk factor for OA. Multiple studies have demonstrated adipokines play a key role in obesity-induced OA. Increasing evidence show that various adipokines may significantly affect the development or clinical course of OA by regulating the pro/anti-inflammatory and anabolic/catabolic balance, matrix remodeling, chondrocyte apoptosis and autophagy, and subchondral bone sclerosis. Several signaling pathways are involved but still have not been systematically investigated. In this article, we review the cellular and molecular mechanisms of adipokines in OA, and highlight the possible signaling pathways. The review suggested adipokines play important roles in obesity-induced OA, and exert downstream function via the activation of various signaling pathways. In addition, some pharmaceuticals targeting these pathways have been applied into ongoing clinical trials and showed encouraging results. However, these signaling pathways are complex and converge into a common network with each other. In the future work, more research is warranted to further investigate how this network works. Moreover, more high quality randomised controlled trials are needed in order to investigate the therapeutic effects of pharmaceuticals against these pathways for the treatment of OA. This review may help researchers to better understand the pathogenesis of OA, so as to provide new insight for future clinical practices and translational research.

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Section: Introductionmentioning

confidence: 99%

Adipokine Signaling Pathways in Osteoarthritis

Zhang

Lin

Yan

et al. 2022

Front. Bioeng. Biotechnol.

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“…Thus, in North America, the rate of adult obesity is ~35 and >70% are overweight, with the rates in children raising as well (discussed in Johnson and Johnson, 2015 ; Colmenarejo, 2020 ; Chrissini and Panagiotakos, 2021 ). In adult onset obesity, there is increased risk for cardiovascular disease (discussed in Budhram-Mahadeo et al, 2021 ; Nabrdalik et al, 2021 ), diabetes (reviewed in Cheng et al, 2021 ), dementia (discussed in Uddin et al, 2021 ), osteoarthritis (reviewed in Midgley, 2020 ; Sun et al, 2020 ), and loss of muscle integrity via infiltration with fat (reviewed in Collins et al, 2018 ). With over 100 genes linked to obesity risk (discussed in Froguel, 2015 ) and multi-generational epigenetic risk as well (discussed in Ahmed, 2010 ; Paul et al, 2019 ), realization of such risks likely may reside in sedentary behavior and poor nutrition associated with high fat high sugar diets of prepared foods (discussed in Collins et al, 2018 ).…”

Section: “Deconditioning” Associated With Obesitymentioning

confidence: 99%

Learning From Human Responses to Deconditioning Environments: Improved Understanding of the “Use It or Lose It” Principle

Hart

2021

Front. Sports Act. Living

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Physical activity, mobility or patterned mobility (i.e., exercise) is intrinsic to the functioning of Homo sapiens, and required for maintenance of health. Thus, systems such as the musculoskeletal and cardiovascular systems appear to require constant reinforcement or conditioning to maintain integrity. Loss of conditioning or development of chronic deconditioning can have multiple consequences. The study of different types of deconditioning and their prevention or reversal can offer a number of clues to the regulation of these systems and point to how deconditioning poses risk for disease development and progression. From the study of deconditioning associated with spaceflight, a condition not predicted by evolution, prolonged bedrest, protracted sedentary behavior, as well as menopause and obesity and their consequences, provide a background to better understand human heterogeneity and how physical fitness may impact the risks for chronic conditions subsequent to the deconditioning. The effectiveness of optimized physical activity and exercise protocols likely depend on the nature of the deconditioning, the sex and genetics of the individual, whether one is addressing prevention of deconditioning-associated disease or disease-associated progression, and whether it is focused on acute or chronic deconditioning associated with different forms of deconditioning. While considerable research effort has gone into preventing deconditioning, the study of the process of deconditioning and its endpoints can provide clues to the regulation of the affected systems and their contributions to human heterogeneity that have been framed by the boundary conditions of Earth during evolution and the “use it or lose it” principle of regulation. Such information regarding heterogeneity that is elaborated by the study of deconditioning environments could enhance the effectiveness of individualized interventions to prevent deconditions or rescue those who have become deconditioned.

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“…More than 90% of patients diagnosed with DM are obese ( Bramante et al, 2017 ). Joint loading due to obesity has been linked to articular cartilage damage in the development and progression of OA ( Bramante et al, 2017 ; Silverstein et al, 2017 ; Sun et al, 2021 ). Increasing age is another known cause for the development of both diseases as adults above the age of 65 are more than twice as likely to develop either condition ( Piva et al, 2015 ; Veronese et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Toward Development of a Diabetic Synovium Culture Model

Sakhrani

Lee

Murphy

et al. 2022

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and inflammation of synovium, the specialized connective tissue that envelops the diarthrodial joint. Type 2 diabetes mellitus (DM) is often found in OA patients, with nearly double the incidence of arthritis reported in patients with diabetes (52%) than those without it (27%). The correlation between OA and DM has been attributed to similar risk factors, namely increasing age and joint loading due to obesity. However, a potential causative link is not well understood due to comorbidities involved with treating diabetic patients, such as high infection rates and poor healing response caused by hyperglycemia and insulin resistance. The purpose of this study was to investigate the effect of hyperglycemic and insulin culture conditions on synovium properties. It was hypothesized that modeling hyperglycemia-induced insulin resistance in synovium would provide novel insights of OA pathogenesis in DM patients. To simulate DM in the synovial joint, healthy synovium was preconditioned in either euglycemic (EG) or hyperglycemic (HG) glucose concentrations with insulin in order to induce the biological response of the diseased phenotype. Synovium biochemical composition was evaluated to determine ECM remodeling under hyperglycemic culture conditions. Concurrent changes in AKT phosphorylation, a signaling pathway implicated in insulin resistance, were measured along with gene expression data for insulin receptors, glucose transporters, and specific glycolysis markers involved in glucose regulation. Since fluid shear stress arising during joint articulation is a relevant upstream stimulus for fibroblast-like synoviocytes (FLS), the predominant cell type in synovium, FLS mechanotransduction was evaluated via intracellular calcium ([Ca2+]i). Incidence and length of primary cilia, a critical effector of cell mechanosensing, were measured as potential mechanisms to support differences in [Ca2+]i responses. Hyperglycemic culture conditions decreased collagen and GAG content compared to EG groups, while insulin recovered ECM constituents. FLS mechanosensitivity was significantly greater in EG and insulin conditions compared to HG and non-insulin treated groups. Hyperglycemic treatment led to decreased incidence and length of primary cilia and decreased AKT phosphorylation, providing possible links to the mechanosensing response and suggesting a potential correlation between glycemic culture conditions, diabetic insulin resistance, and OA development.

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Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

Cited by 40 publications

References 177 publications

Adipokine Signaling Pathways in Osteoarthritis

Adipokine Signaling Pathways in Osteoarthritis

Learning From Human Responses to Deconditioning Environments: Improved Understanding of the “Use It or Lose It” Principle

Toward Development of a Diabetic Synovium Culture Model

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