&lt;p&gt;Overexpression of SOX9 alleviates the progression of human osteoarthritis in vitro and in vivo&lt;/p&gt;

Ouyang, Yuanming; Wang, Wei; Tu, Bing; Zhu, Yi; Fan, Cunyi; Li, Yanfeng

doi:10.2147/dddt.s203974

Cited by 62 publications

(58 citation statements)

References 34 publications

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“…A 2019 study demonstrated that altered expression of SOX9 and runt-related transcription factor 2 was correlated with chondrocyte health, with SOX9 expression being reduced in OA chondrocytes [32]. Importantly, a contemporary study using IL-1β-induced primary human chondrocytes and an OA mouse model showed that overexpression of SOX9 could ameliorate the pathogenesis of OA both in vitro and in vivo [33]. Here, we investigated the effect of agonism of GPR120 on SOX9 expression in ATDC5 chondrocytes and found that GW9508 and TUG 891 significantly rescued IL-1β-induced reduced expression of SOX9.…”

Section: Discussionmentioning

confidence: 99%

Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

Zhang

et al. 2020

Aging

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Osteoarthritis (OA) is a whole-joint disease with extremely high prevalence. In all treatment approaches of OA, blocking the degradation of the cartilage extracellular matrix is an important treatment. In OA, overexpression of derivative enzymes leads to excessive catabolism and reduced synthesis of cartilage including type II collagen and aggrecan, which results in irreversible destruction of the joint. SOX9 is a transcription factor that regulates the synthesis of type II collagen and aggrecan and is significantly downregulated in OA. GPR120 has been reported to affect the pathophysiology of OA. In this study, we used the GPR120 agonist GW9508 and TUG891 in ATDC5 chondrocytes exposed to interleukin (IL)-1β to investigate the involvement of GPR120 in SOX9mediated expression of type II collagen and aggrecan. Our findings show that agonism of GPR120 can reduce inflammation by inhibiting the expression of IL-6 and IL-8 induced by IL-1β. We also show that GW9508 and TUG891 rescue the expression of type II collagen and aggrecan by preventing the reduction of SOX9 expression. Additionally, we demonstrate that the effects of GW9508 on SOX9 expression are mediated through CREB and that GPR120 is indeed required for this effect. Thus, agonism of GPR120 by GW9508 might be a potential therapeutic strategy to halt or prevent cartilage degradation.

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Section: Discussionmentioning

confidence: 99%

Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

Zhang

et al. 2020

Aging

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“…SOX9, as the MR of chondrogenesis, is one of the most crucial TFs for keeping cartilage healthy, and loss of SOX9 is involved in upregulated hypertrophic differentiation, cellular senescence, and decreased ECM production. In vitro, overexpression of SOX9 in CHON-001 chondrocytes resulted in the decreased production of the inflammatory marker TNFα and decreased protein degradation of COL2A1 and SMAD3 [191]. In vivo, overexpression of SOX9 in a surgically induced OA mice model resulted in decreased proteoglycan loss and cartilage destruction, indicating that overexpression of SOX9 might protect against OA.…”

Section: Transcription Factors As Therapeutic Targetsmentioning

confidence: 96%

Transcription Factors in Cartilage Homeostasis and Osteoarthritis

Neefjes

Caam

Kraan

2020

Biology

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Osteoarthritis (OA) is the most common degenerative joint disease, and it is characterized by articular cartilage loss. In part, OA is caused by aberrant anabolic and catabolic activities of the chondrocyte, the only cell type present in cartilage. These chondrocyte activities depend on the intra- and extracellular signals that the cell receives and integrates into gene expression. The key proteins for this integration are transcription factors. A large number of transcription factors exist, and a better understanding of the transcription factors activated by the various signaling pathways active during OA can help us to better understand the complex etiology of OA. In addition, establishing such a profile can help to stratify patients in different subtypes, which can be a very useful approach towards personalized therapy. In this review, we discuss crucial transcription factors for extracellular matrix metabolism, chondrocyte hypertrophy, chondrocyte senescence, and autophagy in chondrocytes. In addition, we discuss how insight into these factors can be used for treatment purposes.

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“…However, Chondrocyte death and matrix loss are discovered in the development of OA [22]. Also, decreased expression of collagen II and SOX9 while increased expression of MMP13 in OA was reported [23]. Interestingly, several recent studies showed that herbs such as setin and scutellarin were found to modulate this process.…”

Section: Discussionmentioning

confidence: 99%

Safflower Yellow a Attenuates Osteoarthritis via Regulating Inflammation and Cholesterol Metabolism

Ju¹,

Tan²,

Liu³

et al. 2020

Preprint

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BackgroundOsteoarthritis (OA) is known to be associated with inflammation and cholesterol metabolism disorder. As a chronic and complex disease, uncovering its molecular mechanism and finding effective therapy with low side effects are urgent. Hydroxysafflor yellow A (HSYA) is extracted from Carthamus tinctorius L, which has extensive pharmacological effects. MethodsIn this study, Interleukin 1β (IL-1β) was used to establish the OA model in vitro, and the impacts of HSYA on the OA cell model were analyzed. We used CCK-8 to measure the cell viability and Flow Cytometry to test the apoptosis. ELISA was performed to calculate the release of inflammatory cytokines. And WB was carried out to measure the expression of collagen and cholesterol relevant proteins. We also measured the protein levels in NF-κB and PI3K/Akt/mTOR signaling pathways. ResultsThe results showed that HSYA promoted cell viability and inhibited apoptosis. And it up-regulated the expression levels of collagen II (Col-II) and Sry related HMG box-9 (SOX9) while down-regulated the expression of matrix metalloproteinase-13 (MMP13). The IL-1β induced high levels of IL-6 and TNF-α were inhibited by HSYA. Also, HSYA regulated the expression of cholesterol relevant proteins. Compared with the model group, the levels of APT-binding cassette transporter 1 (ABCA1) and cholesterol transport gene (APOA-1) were significantly elevated. However, the levels of cholesterol-processing enzymes cholesterol 25-hydroxylase (CH25H) and 25-hydroxy-cholesterol 7-alpha- hydroxylase (CYP7B1) were inhibited. Besides, HSYA inhibited the protein expression in NF-κB and PI3K/Akt/mTOR signaling pathways. ConclusionsHSYA was proved to regulate inflammatory response and cholesterol metabolism in vitro.

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<p>Overexpression of SOX9 alleviates the progression of human osteoarthritis in vitro and in vivo</p>

Cited by 62 publications

References 34 publications

Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

Transcription Factors in Cartilage Homeostasis and Osteoarthritis

Safflower Yellow a Attenuates Osteoarthritis via Regulating Inflammation and Cholesterol Metabolism

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