Osteoarthritic Infrapatellar Fat Pad Aggravates Cartilage Degradation via Activation of p38MAPK and ERK1/2 Pathways

Zhou, Zhilai; Tang, Simin; Nie, Xiaoyu; Zhang, Yiqun; Li, Delong; Zhao, Yang; Cao, Yumei; Yin, Jianwen; Chen, Tianyu; Ruan, Guangfeng; Zhu, Zhaohua; Bai, Xiaochun; Han, Weiyu; Ding, Changhai

doi:10.21203/rs.3.rs-98317/v1

Cited by 2 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The culture protocol of cartilage explants was described in our previous study ( 51 ). Briefly, fresh human cartilage was separated from the subchondral bone, cut into small pieces (5 mm by 5 mm by 2 mm), and randomly divided into indicated groups for PILA knockdown and overexpression.…”

Section: Methodsmentioning

confidence: 99%

The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1

et al. 2022

View full text Add to dashboard Cite

Inflammatory cytokine–induced activation of nuclear factor κB (NF-κB) signaling plays a critical role in the pathogenesis of osteoarthritis (OA). We identified PILA as a long noncoding RNA (lncRNA) that enhances NF-κB signaling and OA. The abundance of PILA was increased in damaged cartilage from patients with OA and in human articular chondrocytes stimulated with the proinflammatory cytokine tumor necrosis factor (TNF). Knockdown of PILA inhibited TNF-induced NF-κB signaling, extracellular matrix catabolism, and apoptosis in chondrocytes, whereas ectopic expression of PILA promoted NF-κB signaling and matrix degradation. PILA promoted PRMT1-mediated arginine methylation of DExH-box helicase 9 (DHX9), leading to an increase in the transcription of the gene encoding transforming growth factor β–activated kinase 1 (TAK1), an upstream activator of NF-κB signaling. Furthermore, intra-articular injection of an adenovirus vector encoding PILA triggered spontaneous cartilage loss and exacerbated posttraumatic OA in mice. This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.

show abstract

Section: Methodsmentioning

confidence: 99%

The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In addition, 30 cartilage specimens and clinical data of patients with knee OA who underwent total knee arthroplasty were collected and divided into the undamaged (ICRS = 0) and damaged (ICRS = 1-4) groups according to the International Cartilage Repair Society (ICRS) grading system [24]. Chondrocytes, infrapatellar fat pad cells [25], meniscus cells [26], anterior cruciate ligament cells [27], and synovial membrane cells [28] were isolated and cultured as previously described.…”

Section: Patient Recruitment Sample Collection and Cellmentioning

confidence: 99%

tRNA-Derived Fragment tRF-5009A Regulates Autophagy and Degeneration of Cartilage in Osteoarthritis via Targeting mTOR

Deng

Long

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

tRNA-derived fragments (tRFs) have been reported to have critical regulatory roles in osteoarthritis (OA). Recent studies have suggested that autophagy promotes the homeostasis of the extracellular matrix of chondrocytes in OA. However, the role of tRFs in posttranscriptional gene regulation during autophagy in OA is unknown. Therefore, we explored the role of tRF-5009A in the posttranscriptional gene regulation of autophagy and cartilage degeneration in OA. Using RNA sequencing, we identified tRF-5009A, the tRNAValCAC-derived fragment, in OA tissues and explored its expression by quantitative reverse transcription PCR and fluorescence in situ hybridization. We further investigated the relationship between the expression of tRF-5009A and clinical factors in OA. Chondrocytes were transfected with a tRF-5009A inhibitor or mimic to determine their functions, including in relation to autophagy and the cartilage phenotype. A rescue experiment and dual-luciferase reporter assay were conducted to determine whether the 3 ′ -untranslated region (UTR) of mTOR contains a tRF-5009A-binding site. tRF-5009A was downregulated in the cartilage of OA knees, especially in damaged areas. mTOR was highly expressed in damaged cartilage and negatively correlated with the expression of tRF-5009A; transfection with a tRF-5009A inhibitor promoted the expression of mTOR and suppressed autophagy, whereas transfection with a tRF-5009A mimic had the opposite effect. A dual-luciferase reporter assay showed that tRF-5009A silenced the expression of mTOR by binding to its 3 ′ -UTR. Thus, tRF-5009A regulates autophagy and cartilage degeneration in OA by targeting mTOR. In summary, these findings provide an additional tool for the clinical diagnosis and novel targeted therapy of OA.

show abstract

Osteoarthritic Infrapatellar Fat Pad Aggravates Cartilage Degradation via Activation of p38MAPK and ERK1/2 Pathways

Cited by 2 publications

References 23 publications

The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1

The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1

tRNA-Derived Fragment tRF-5009A Regulates Autophagy and Degeneration of Cartilage in Osteoarthritis via Targeting mTOR

Contact Info

Product

Resources

About