logo logo
Overexpression of circAtp9b in ulcerative colitis is induced by lipopolysaccharides and upregulates PTEN to promote the apoptosis of colonic epithelial cells. Li Fengdong,Fu Jinjin,Fan Li,Lu Shuangshuang,Zhang Huahui,Wang Xiaoying,Liu Zhanju Experimental and therapeutic medicine It has been reported that knockdown of circular RNA (circ) ATPase class II type 9B (Atp9b) can reduce lipopolysaccharide (LPS)-induced inflammation, which plays a notable role in ulcerative colitis (UC). The present study aimed to explore the role of circAtp9b in UC. The expression levels of Atp9b and PTEN in the plasma of patients with UC (n=60) and healthy controls (n=60) were determined via reverse transcription-quantitative PCR. Overexpression of circAtp9b and PTEN were achieved in human colonic epithelial cells (HCnEpCs) to explore the relationship between circAtp9b and PTEN. The role of circAtp9b and PTEN in regulating the apoptosis of HCnEpCs under LPS treatment was evaluated using flow cytometry. The present study revealed that circAtp9b was upregulated in UC and that it was positively correlated with PTEN. In HCnEpCs, LPS treatment resulted in upregulation of circAtp9b in a dose-dependent manner. Moreover, overexpression of circAtp9b mediated the upregulation of PTEN in HCnEpCs, while silencing of circAtp9b decreased the expression levels of PTEN. Apoptosis analysis demonstrated that overexpression of circAtp9b and PTEN promoted the apoptosis of HCnEpCs. In addition, silencing of circAtp9b suppressed apoptosis. Moreover, overexpression of PTEN reduced the effects of silencing of circAtp9b. In conclusion, overexpression of circAtp9b in UC was induced by LPS and it positively upregulated PTEN to promote the apoptosis of HCnEpCs induced by LPS. 10.3892/etm.2021.10840
circAtp9b knockdown alleviates LPS-caused inflammation provided that microRNA-27a is upregulated. Sun Jianwei,Wang Xijuan,Wang Dandan,Zhao Ziyan,Zhang Lei,Zhang Jiajie International immunopharmacology BACKGROUND:The etiology of pneumonia is associated with gram-negative bacteria in malnourished children. To anatomize the molecular mechanisms, we focused on the modulatory function of circular RNA-Atp9b (circAtp9b) on inflammation in which microRNA-27a (miR-27a) might be implicated. METHODS:MRC-5 cells were stimulated by lipopolysaccharide (LPS) to exhibit inflammatory lesions assessed by viability and apoptosis as well as the cleavage of caspase-3, production of interleukin-6 and tumor necrosis factor alpha, and generation of reactive oxygen species (ROS). circAtp9b and miR-27a were quantified by qRT-PCR. circAtp9b- or miR-27a-silenced MRC-5 cells were established to study their roles in inflammation. Moreover, the change of NF-κB and JNK pathways was monitored. RESULTS:LPS was observed to induce adverse inflammatory injuries by repressing viability and fortified apoptosis with cleavage of caspase-3, production of cytokines, formation of ROS and abundance of circAtp9b. The results suggested circAtp9b silence prevented MRC-5 cells from LPS-elicited insults, which was accompanied by blockage of NF-κB and JNK. circAtp9b silence restored miR-27a which was repressed by LPS. miR-27a knockdown abrogated the protective capacities of circAtp9b silence with activation of NF-κB and JNK in response to LPS. CONCLUSION:LPS triggered adverse inflammation response by elevating the biogenesis of circAtp9b which caused a repressive role in miR-27a expression. 10.1016/j.intimp.2019.105925
LPS-inducible circAtp9b is highly expressed in osteoporosis and promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a. Feng Yinan,Ding Li,Li Longguang Journal of orthopaedic surgery and research BACKGROUND:Circular RNA circAtp9b is an enhancer of LPS-induced inflammation, which promotes osteoporosis (OS). This study explored the role of circAtp9b in OS. METHODS:RT-qPCR was performed to detect the expression of circAtp9b and microRNA (miR)-17-92a (both mature and premature) in OS and healthy controls. The subcellular location of circAtp9b was assessed by nuclear fractionation assay. The direct interaction between circAtp9b and premature miR-17-92a was detected by RNA pull-down assay. The role of circAtp9b in regulating the maturation of miR-17-92a in osteoblasts was explored by overexpression assay and RT-qPCR. Cell apoptosis was analyzed by cell apoptosis assay. RESULTS:OS patients exhibited upregulation of circAtp9b and premature miR-17-92a, but downregulation of mature miR-17-92a. In osteoblasts, circAtp9b suppressed the maturation of miR-17-92a. LPS upregulated circAtp9b and premature miR-17-92a, and downregulated mature miR-17-92a in osteoblasts. CircAtp9b was detected in both nucleus and cytoplasm, and it directly interacted with premature miR-17-92a. Overexpression of circAtp9b reduced the effects of miR-17-92a on the apoptosis of osteoblasts induced by LPS. CONCLUSION:CircAtp9b is LPS-inducible and upregulation of circAtp9b in OS promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a. 10.1186/s13018-022-03072-x
Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis. Musumeci Giuseppe,Castrogiovanni Paola,Trovato Francesca Maria,Weinberg Annelie Martina,Al-Wasiyah Mohammad K,Alqahtani Mohammed H,Mobasheri Ali International journal of molecular sciences Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA. 10.3390/ijms160920560
The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression. Rim Yeri Alice,Nam Yoojun,Ju Ji Hyeon International journal of molecular sciences Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiation and progression of OA. Although chondrocyte hypertrophy and cell death are both crucial steps during the natural process of endochondral bone formation, the abnormal activation of these two processes after injury or during aging seems to accelerate the progression of OA. However, the exact mechanisms of OA progression and these two processes remain poorly understood. Chondrocyte senescence and hypertrophy during OA share various markers and processes. In this study, we reviewed the changes that occur during chondrocyte hypertrophy or senescence in OA and the attempts that were made to regulate them. Regulation of hypertrophic or senescent chondrocytes might be a potential therapeutic target to slow down or stop OA progression; thus, a better understanding of the processes is required for management. 10.3390/ijms21072358
Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. International journal of molecular sciences Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance between anabolic and katabolic processes is a well-established factor. The complex network of cytokines regulating these processes and cell communication has a central role in the development and progression of osteoarthritis. Concentrations of both proinflammatory and anti-inflammatory cytokines were found to be altered depending on the osteoarthritis stage and activity. In this review, we analyzed individual cytokines involved in the immune processes with an emphasis on their function in osteoarthritis. 10.3390/ijms22179208
Chondrocyte dedifferentiation and osteoarthritis (OA). Charlier Edith,Deroyer Céline,Ciregia Federica,Malaise Olivier,Neuville Sophie,Plener Zelda,Malaise Michel,de Seny Dominique Biochemical pharmacology Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage degradation but also synovial membrane inflammation, osteophyte formation and subchondral bone sclerosis. Medical care is mainly based on alleviating pain symptoms, but to date, no effective drug can stop the disease progression. Cartilage is a tissue composed of only one cell type, chondrocytes, wrapped in a collagen rich extracellular matrix they synthesize. Chondrocytes can adopt different phenotypes in vivo and in vitro, defined by the collagen type they produce. Isolated from their matrix, chondrocytes present the particularity to dedifferentiate, producing fibroblastic type I and III collagens. With OA onset, chondrocytes undergo multiple changes, in terms of proliferation, viability, but also secretory profile. The acquisition of a hypertrophic phenotype (producing aberrant type X collagen and catabolic MMP-13 protease) by chondrocytes is well documented and contributes to OA development. However, it is increasingly believed that chondrocytes rather acquire a variety of degenerated phenotypes at the onset of OA, including a "dedifferentiated-like" phenotype that might also contribute to OA progression. In this review, we will (i) present molecular knowledge underlying dedifferentiation process, (ii) emphasize connections between dedifferentiation and OA and (iii) consider OA therapeutic strategies aiming at the maintenance of chondrogenic phenotype. 10.1016/j.bcp.2019.02.036