Etoricoxib decreases subchondral bone mass and attenuates biomechanical properties at the early stage of osteoarthritis in a mouse model

Liu, Bo; Ji, Chenchen; Shao, Yijie; Liang, Ting; He, Jiaheng; Jiang, Hongjuan; Chen, Guangdong; Luo, Zong‐Ping

doi:10.1016/j.biopha.2020.110144

Cited by 15 publications

(10 citation statements)

References 49 publications

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“…These study results were consistent with a previous study which showed that subchondral bone loss is in the DMM OA model [ 40 ]. On the contrary, some studies had found that trabecular bone volume/tissue volume (BV/TV) and tibial thickness increased in the subchondral bone of the DMM model [ 41 , 42 ]. PRMT5 has been demonstrated to regulate osteoclast differentiation and protect against the bone-related effects of ovariectomy in our previous study [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling

et al. 2020

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Objectives A role for the type II arginine methyltransferase PRMT5 in various human diseases has been identified. In this study, the potential mechanism underlying the involvement of PRMT5 in the pathological process leading to osteoarthritis (OA) was investigated. Methods PRMT5 expression in cartilage tissues from patients with OA and control individuals was assessed by immunohistochemical staining. The regulatory and functional roles of PRMT5 in the chondrocytes of patients with OA and control individuals were determined by western blotting and reverse transcription polymerase chain reaction. The effects of the PRMT5 inhibitor EPZ on interleukin-1β-induced inflammation were examined in the chondrocytes of patients with OA and in the destabilized medial meniscus (DMM) of a mouse model of OA. Results PRMT5 was specifically upregulated in the cartilage of patients with OA. Moreover, adenovirus-mediated overexpression of PRMT5 in human chondrocytes caused cartilage degeneration. This degeneration was induced by elevated expression levels of matrix-degrading enzymes (matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13)) in chondrocytes. The activation of the MAPK and nuclear factor κB signaling pathways was evidenced by elevated levels of p-p65, p-p38, and p-JNK. These effects were attenuated by inhibiting the expression of PRMT5. In the mouse model, EPZ inhibited PRMT5 expression, thus protecting mouse cartilage from DMM-induced OA. Conclusions Our results demonstrate that PRMT5 is a crucial regulator of OA pathogenesis, implying that EPZ has therapeutic value in the treatment of this cartilage-destroying disease.

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Section: Discussionmentioning

confidence: 99%

PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling

et al. 2020

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“…A total of sixty 10–12-week-old C57BL/6 male mice from the Animal Center of Chinese Academy of Sciences Shanghai, China, were used in the study. The OA mouse model was established using surgical destabilization of the medial meniscus (DMM), as previously described (Liu 2020 ). These mice were randomly divided into three groups, namely the sham group, DMM group, and DMM + DSS group, with 10 mice per group.…”

Section: Methodsmentioning

confidence: 99%

Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

Zhang

et al. 2021

Mol Med

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Purpose Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1β is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1β-induced inflammatory responses in OA. Methods IL-1β was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. Results DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1β treated chondrocytes. In addition, DSS downregulated IL-1β-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1β-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. Conclusions Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

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“…The scanned images were processed and recombined using the NRecon and DataView software. The cartilaginous layers of the ankle and subtalar joints and 10 consecutive layers from the region of interest (ROI) were selected for quantitative analysis in the CTAN software, then three-dimensional reconstruction was performed using the Mimics 15.0 software (Materialise, Belgium) [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

A mouse model of ankle-subtalar joint complex instability induced post-traumatic osteoarthritis

et al. 2021

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Background Ankle-subtalar joint complex instability is not uncommonly presented in the clinic, but symptoms and signs similar to other conditions can easily lead to its misdiagnosis. Due to the lack of appropriate animal models, research on ankle-subtalar joint complex instability is limited. The aims of the present study were to establish an animal model of ankle-subtalar joint complex instability in mice and to explore its relationship with post-traumatic osteoarthritis (PTOA). Methods Twenty-one male C57BL/6J mice were randomly divided into three groups: SHAM group (sham surgery group), transected cervical ligament + anterior talofibular ligament (CL+ATFL) group, and transected cervical ligament + deltoid ligament (CL+DL) group. Two weeks after surgery, all mice underwent cage running training. Balance beam and gait tests were used to evaluate the changes in self-movement in the mice after ankle-subtalar ligament injury. Micro-CT and histological staining were used to evaluate the progress of PTOA. Results Compared with the SHAM group, balance and gait were affected in the ligament transection group. Twelve weeks after surgery, the time required to cross the balance beam in the CL+ATFL group was 35.1% longer and the mice slipped 3.6-fold more often than before surgery, and the mean step length on the right side was 7.2% smaller than that in the SHAM group. The time required to cross the balance beam in the CL+DL group was 32.1% longer and the mice slipped 3-fold more often than prior to surgery, and the average step length on the right side was 5.6% smaller than that in the SHAM group. CT images indicated that 28.6% of the mice in the CL+DL group displayed dislocation of the talus. Tissue staining suggested that articular cartilage degeneration occurred in mice with ligament transection 12 weeks after surgery. Conclusions Transected mice in the CL+ATFL and CL+DL groups displayed mechanical instability of the ankle-subtalar joint complex, and some mice in the CL+DL group also suffered from talus dislocation due to ligament injury leading to loss of stability of the bone structure. In addition, as time progressed, the articular cartilage displayed degenerative changes, which affected the ability of animals to move normally.

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Etoricoxib decreases subchondral bone mass and attenuates biomechanical properties at the early stage of osteoarthritis in a mouse model

Cited by 15 publications

References 49 publications

PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling

PRMT5 inhibition attenuates cartilage degradation by reducing MAPK and NF-κB signaling

Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

A mouse model of ankle-subtalar joint complex instability induced post-traumatic osteoarthritis

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