Activation of the kynurenine–aryl hydrocarbon receptor axis impairs the chondrogenic and chondroprotective effects of human umbilical cord-derived mesenchymal stromal cells in osteoarthritis rats

Wang, Xinwei; Zhao, Yingjie; Li, Susu; Wang, Yueye; Jia, Chengyan; Yang, Xiaofang; Li, Siyu; Zhang, Bingjie; Wei, Wei; Chang, Yan

doi:10.1007/s13577-022-00811-4

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…Lögters et al [ 37 ] found that kynurenine could inhibit chondrocyte (ATDC5) cell proliferation in a dose-dependent way. In OA rat models, Wang et al [ 38 ] found that activation of the kynurenine-aryl hydrocarbon receptor axis can impair chondrogenesis and chondroprotection in human umbilical cord-derived mesenchymal stromal cells. Based on the given evidence and our findings, kynurenine can be considered an important circulation biomarker and a key therapeutic target for OA.…”

Section: Discussionmentioning

confidence: 99%

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study

Gu,

Jin,

et al. 2023

J Transl Med

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Background Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases and is the leading cause of pain and disability in the aged population. However, the underlying biological mechanism has not been fully understood. This study aims to reveal the causal effect of circulation metabolites on OA susceptibility. Methods A two-sample Mendelian Randomization (MR) analysis was performed to estimate the causality of GDMs on OA. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas 8 different OA phenotypes, including any-site OA (All OA), knee and/or hip OA (knee/hip OA), knee OA, hip OA, spine OA, finger and/or thumb OA (hand OA), finger OA, thumb OA, were set the outcomes. Inverse-variance weighted (IVW) was used for calculating causal estimates. Methods including weight mode, weight median, MR-egger, and MR-PRESSO were used for the sensitive analysis. Furthermore, metabolic pathway analysis was performed via the web-based Metaconflict 4.0. All statistical analyses were performed in R software. Results In this MR analysis, a total of 235 causative associations between metabolites and different OA phenotypes were observed. After false discovery rate (FDR) correction and sensitive analysis, 9 robust causative associations between 7 metabolites (e.g., arginine, kynurenine, and isovalerylcarnitine) and 5 OA phenotypes were finally identified. Additionally, eleven significant metabolic pathways in 4 OA phenotypes were identified by metabolic pathway analysis. Conclusion The finding of our study suggested that identified metabolites and metabolic pathways can be considered useful circulating metabolic biomarkers for OA screening and prevention in clinical practice, and can also serve as candidate molecules for future mechanism exploration and drug target selection.

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Section: Discussionmentioning

confidence: 99%

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study

Gu,

Jin,

et al. 2023

J Transl Med

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“…Small animal models of OA have the advantage of allowing larger sample size, less animal housing space requirement, and reduced cost versus larger animal models ( Mukherjee et al, 2022 ). Small animal models of OA include mouse, rat, guinea pig and rabbit ( Sato et al, 2012 ; Toghraie et al, 2012 ; ter Huurne et al, 2012 ; van Buul et al, 2014 ; Kim et al, 2014 ; Singh et al, 2014 ; Deng et al, 2015 ; Kuroda et al, 2015 ; Saulnier et al, 2015 ; Wang et al, 2015 ; Yang et al, 2015 ; Chiang et al, 2016 ; Hermeto et al, 2016 ; Latief et al, 2016 ; Li et al, 2016 ; Morille et al, 2016 ; Ozeki et al, 2016 ; Mei et al, 2017a ; Mei et al, 2017b ; Parrilli et al, 2017 ; Chang et al, 2018 ; Choi et al, 2018 ; Desando et al, 2018 ; Fan et al, 2018 ; Neybecker et al, 2018 ; Cheng et al, 2019 ; Desando et al, 2019 ; Mahmoud et al, 2019 ; McKinney et al, 2019 ; Vinod et al, 2019 ; Zhou et al, 2019 ; Jeon et al, 2020 ; Tong et al, 2020 ; Wang et al, 2020 ; Xing et al, 2020 ; Zhi et al, 2020 ; Tang et al, 2021 ; Xing et al, 2021 ; Juskovic et al, 2022 ; Kwapisz et al, 2022 ; Wang et al, 2023 ) ( Table 2 ). Techniques to initiate OA include anterior cruciate transection (ACLT), ACLT with destabilization of the medial meniscus (DMM), chemically- (e.g., Mono-iodoacetate [MIA] or papain intraarticular injection) or collagenase-induced, as well as spontaneous OA ( Culley et al, 2015 ).…”

Section: Animal Models Of Osteoarthritismentioning

confidence: 99%

“…Contrary to OCD, the entire articular surface may be involved, and must be considered when initiating a treatment. In order to treat the entire articular surface, investigators have largely relied on fluid-based vehicles to deliver their regenerative biological elements, including saline/PBS, serum, and media ( Toghraie et al, 2012 ; ter Huurne et al, 2012 ; van Buul et al, 2014 ; Singh et al, 2014 ; Saulnier et al, 2015 ; Yang et al, 2015 ; Latief et al, 2016 ; Li et al, 2016 ; Ozeki et al, 2016 ; Mei et al, 2017b ; Chang et al, 2018 ; Choi et al, 2018 ; Fan et al, 2018 ; Neybecker et al, 2018 ; Cheng et al, 2019 ; Desando et al, 2019 ; Mahmoud et al, 2019 ; Zhou et al, 2019 ; Jeon et al, 2020 ; Tong et al, 2020 ; Zhi et al, 2020 ; Tang et al, 2021 ; Xing et al, 2021 ; Juskovic et al, 2022 ; Wang et al, 2023 ) ( Table 2 ; Figure 1 ). More recently, HA has become commonly used ( Sato et al, 2012 ; Deng et al, 2015 ; Kuroda et al, 2015 ; Wang et al, 2015 ; Chiang et al, 2016 ; Vinod et al, 2019 ; Wang et al, 2020 ; Xing et al, 2020 ; Kwapisz et al, 2022 ).…”

Section: Animal Models Of Osteoarthritismentioning

confidence: 99%

Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair—a narrative review

Campbell,

Trudel

2024

Front. Bioeng. Biotechnol.

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Focal cartilage defects are common in youth and older adults, cause significant morbidity and constitute a major risk factor for developing osteoarthritis (OA). OA is the most common musculoskeletal (MSK) disease worldwide, resulting in pain, stiffness, loss of function, and is currently irreversible. Research into the optimal regenerative approach and methods in the setting of either focal cartilage defects and/or OA holds to the ideal of resolving both diseases. The two fundamentals required for cartilage regenerative treatment are 1) the biological element contributing to the regeneration (e.g., direct application of stem cells, or of an exogenous secretome), and 2) the vehicle by which the biological element is suspended and delivered. The vehicle provides support to the regenerative process by providing a protective environment, a structure that allows cell adherence and migration, and a source of growth and regenerative factors that can activate and sustain regeneration. Models of cartilage diseases include osteochondral defect (OCD) (which usually involve one focal lesion), or OA (which involves a more diffuse articular cartilage loss). Given the differing nature of these models, the optimal regenerative strategy to treat different cartilage diseases may not be universal. This could potentially impact the translatability of a successful approach in one condition to that of the other. An analogy would be the repair of a pothole (OCD) versus repaving the entire road (OA). In this narrative review, we explore the existing literature evaluating cartilage regeneration approaches for OCD and OA in animal then in human studies and the vehicles used for each of these two conditions. We then highlight strengths and challenges faced by the different approaches presented and discuss what might constitute the optimal cartilage regenerative delivery vehicle for clinical cartilage regeneration.

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Causal factors for osteoarthritis risk revealed by mendelian randomization analysis

Luo,

Zhang,

Yang

et al. 2024

Aging Clin Exp Res

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Osteoarthritis (OA), a prevalent chronic disease among the elderly, presents a complex pathogenesis and currently lacks effective treatment. Traditional observational studies are time-consuming, labor-intensive, susceptible to confounding factors, and cannot establish causal relationships. Mendelian randomization (MR) analysis, leveraging genetic variation to assess causal associations between exposures and outcomes, offers a cost-effective and efficient alternative. Over the past decade, large-scale genome-wide association studies have identified numerous genetic variants linked to OA risk factors, facilitating MR study design. In this review, we systematically identified 52 MR studies meeting specific criteria and evaluated their quality, exploring the impact of lifestyle, nutrition, comorbidities, circulating metabolites, plasma proteins, and other health factors on OA risk. We discuss the results and potential mechanisms of MR findings, addressing conflicting evidence based on existing literature and our prior research. With the ongoing expansion of genome-wide association data, we anticipate MR’s role in future OA studies to broaden, particularly in drug development research using targeted MR approaches. We thus aim for this paper to offer valuable insights for researchers and clinicians in related fields.

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Activation of the kynurenine–aryl hydrocarbon receptor axis impairs the chondrogenic and chondroprotective effects of human umbilical cord-derived mesenchymal stromal cells in osteoarthritis rats

Cited by 4 publications

References 43 publications

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study

Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study

Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair—a narrative review

Causal factors for osteoarthritis risk revealed by mendelian randomization analysis

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