Decreased RIPK1 expression in chondrocytes alleviates osteoarthritis via the TRIF/MyD88-RIPK1-TRAF2 negative feedback loop

Liang, Shuang; Wang, Zhenggang; Zhang, Zhenzhen; Lv, Zheng‐tao; Wang, Yuting; Peng, Cheng; Sun, Kai; Yang, Qing; Chen, Anmin

doi:10.18632/aging.102354

Cited by 19 publications

(16 citation statements)

References 55 publications

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“…Multiple studies have shown that subchondral bone plays a critical role in the occurrence and development of OA [35,36]. Remodeling of subchondral bone is an important part of the progression of OA [37,38]. Nakasa et al [39] showed that subchondral sclerosis of the tibia could be observed 7 days after DMM, which was consistent with the findings of our study.…”

Section: Discussionsupporting

confidence: 91%

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

Liu¹,

Ji²,

Shao³

et al. 2020

Preprint

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BackgroundEtoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief. The purpose of our study was to investigate the effects of Etoricoxib on mouse subchondral bone in early OA.MethodsOA was induced via destabilization of the medial meniscus (DMM) in C57BL/6J mice. After surgery, the mice were randomly and equally divided into five groups: a sham-operated control group (Sham group), an osteoarthritis (OA) group (DMM group), an OA treated with Etoricoxib 5mg/kg (DMM+E5) group, an OA treated with Etoricoxib 10mg/kg (DMM+E10) group, and an OA treated with Etoricoxib 20mg/kg (DMM+E20) group. Mice in the Sham group and DMM group were injected with a similar dose of vehicle (40% ethyl alcohol–saline solution). Four weeks after treatment, mice were euthanized. Micro computed tomography (Mirco-CT) analysis, Safranin O-Fast Green staining, hematoxylin and eosin (HE) staining were performed to evaluate morphological and structural changes. In addition, atomic force microscopy (AFM) analysis was performed to evaluate changes in the elastic modulus. Furthermore, changes in microstructure were detected by scanning electron microscopy (SEM).ResultsEtoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Furthermore, exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. In cartilage and synovium, Etoricoxib did not significantly change the Osteoarthritis Research Society International (OARSI) score, the modified Mankin score, and the synovialitis-score versus the DMM group. ConclusionOur results demonstrate that although Etoricoxib can relieve the pain induced by OA, it also has adverse effects on subchondral bone in early OA.

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Section: Discussionsupporting

confidence: 91%

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

Liu¹,

Ji²,

Shao³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Multiple studies have shown that subchondral bone plays a critical role in the occurrence and development of OA [35,36]. Remodeling of subchondral bone is an important part of the progression of OA [37,38]. Nakasa T et al [39] showed that subchondral sclerosis of the tibia could be observed 7 days after DMM, which was consistent with the findings of our study.…”

Section: Discussionsupporting

confidence: 91%

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

Liu

Shao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Etoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief. The purpose of our study was to investigate the effects of Etoricoxib on mouse subchondral bone in early OA. Methods OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6J mice. After surgery, the mice were randomly and equally divided into five groups: a sham-operated control group (Sham group), an osteoarthritis (OA) group (DMM group), an OA treated with Etoricoxib 5mg/kg (DMM+E5) group, an OA treated with Etoricoxib 10mg/kg (DMM+E10) group, and an OA treated with Etoricoxib 20mg/kg (DMM+E20) group. Mice in the Sham group and DMM group were injected with a similar dose of vehicle (40% ethyl alcohol–saline solution). Four weeks after treatment, mice were euthanized. Micro computed tomography (Mirco-CT) analysis, Safranin O-Fast Green staining, hematoxylin and eosin (HE) staining were performed to evaluate morphological and structural changes. In addition, atomic force microscopy (AFM) analysis was performed to evaluate changes in the elastic modulus. Furthermore, changes in microstructure were detected by scanning electron microscopy (SEM). Results Etoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Furthermore, exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. In cartilage and synovium, Etoricoxib did not significantly change the Osteoarthritis Research Society International (OARSI) score, the modified Mankin score, and the synovialitis-score versus the DMM group. Conclusion Although Etoricoxib can relieve the pain induced by OA, it can also change microstructures and biomechanical properties of the subchondral bone at the early stage of OA, cause osteoporotic changes in subchondral bone structure, increase the risk of fragile fracture of subchondral bone.

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“…The NF-кB pathway promoted the expression of OArelated proteins, such as RUNX2 and VEGF 17,18,20,34 . Many studies have confirmed that MYD88 played an important role in the OA process in recent years [35][36][37][38][39] . Here, modulation of miR-665 and circRNF121 resulted in altered MYD88 expression.…”

Section: Discussionmentioning

confidence: 91%

LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway

Wang¹,

Hao²,

Liu³

et al. 2020

Cell Death Dis

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Osteoarthritis (OA) is a joint disease that causes great pain to patients and imposes a tremendous burden on the world's medical resources. Regulatory noncoding RNAs, including circular RNAs (circRNAs) and microRNAs (miRNAs), play an important role in OA progression. Here, we identified differential expression of transcription factor LEF1 that increased circRNA circRNF121 levels in normal and OA cartilage tissues. The expression of LEF1 and circRNF121 was positively associated with Mankin's scores. Alteration of circRNF121 mediated the degradation of extracellular mechanisms (ECM), apoptosis, and proliferation of chondrocytes. MiR-665 was identified as a direct regulatory target of circRNF121 and MYD88. Functional analysis showed that circRNF121 and MYD88 modulated ECM degradation, apoptosis, and proliferation of chondrocytes, which could be reversed by miR-665. MYD88 regulated the activity of the NF-кB signaling pathway by circRNF121 via sponging miR-665. Collectively, these data indicated that LEF1 impacted OA progression by modulating the circRNF121/miR-665/MYD88 axis via NF-кB pathway. Our research proposed a new molecular mechanism for the development of OA, and provided a prospective therapeutic target for OA.

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Decreased RIPK1 expression in chondrocytes alleviates osteoarthritis via the TRIF/MyD88-RIPK1-TRAF2 negative feedback loop

Cited by 19 publications

References 55 publications

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-кB signaling pathway

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