Dicalcium silicate microparticles modulate the differential expression of circRNAs and mRNAs in BMSCs and promote osteogenesis <i>via</i> circ_1983–miR-6931–Gas7 interaction

Zhong, Wenchao; Li, Xingyang; Pathak, Janak L.; Chen, Liangjiao; Cao, Weimin; Zhu, Mingjing; Luo, Qiaojie; Wu, Antong; Chen, Yunxin; Yi, Lingbo; Ma, Manyuan; Zhang, Qingbin

doi:10.1039/d0bm00459f

Cited by 19 publications

(18 citation statements)

References 55 publications

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“…Last but not least, COL6A3/ACTG1 ( Li et al, 2020a ) and fibronectin1 (FN1) ( Wu et al, 2020a ) were found involved in fibroblast transformation. Although many catabolic genes have been found, there are very limited key anabolic genes that can promote the proliferation or differentiation of chondrocytes or encode key anchoring collagen molecules and the corresponding genes including GDF5 ( Sun et al, 2021 ), Gas7 ( Zhong et al, 2020 ), PRELP ( Li et al, 2019a ), TGF-β ( Tao et al, 2016 ), SOX9 ( Tao et al, 2016 ), and COL9A1 ( Durand et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

Deng

Zong

et al. 2021

Front. Pharmacol.

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Osteoarthritis (OA) is a degenerative joint disease in the musculoskeletal system with a relatively high incidence and disability rate in the elderly. It is characterized by the degradation of articular cartilage, inflammation of the synovial membrane, and abnormal structure in the periarticular and subchondral bones. Although progress has been made in uncovering the molecular mechanism, the etiology of OA is still complicated and unclear. Nevertheless, there is no treatment method that can effectively prevent or reverse the deterioration of cartilage and bone structure. In recent years, in the field of pharmacology, research focus has shifted to disease prevention and early treatment rather than disease modification in OA. Biologic agents become more and more attractive as their direct or indirect intervention effects on the initiation or development of OA. In this review, we will discuss a wide spectrum of biologic agents ranging from DNA, noncoding RNA, exosome, platelet-rich plasma (PRP), to protein. We searched for key words such as OA, DNA, gene, RNA, exosome, PRP, protein, and so on. From the pharmacological aspect, stem cell therapy is a very special technique, which is not included in this review. The literatures ranging from January 2016 to August 2021 were included and summarized. In this review, we aim to help readers have a complete and precise understanding of the current pharmacological research progress in the intervention of OA from the biological aspect and provide an indication for the future translational studies.

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Section: Methodsmentioning

confidence: 99%

Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

Deng

Zong

et al. 2021

Front. Pharmacol.

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“…It has been revealed that a correlation exists between c i r c R N A s a n d W n t s i g n a l i n g d u r i n g o s t e o g e n i c differentiation. The sequencing of circRNAs and mRNAs were performed in several studies in which bioinformatic analyses showed the possible involvement of Wnt signaling (32,69). Additionally, circ19142 and circ5846, two circRNAs that are significantly upregulated in BMP-2induced MC3T3-E1 cells, were predicted to target miR-7067-5p (34).…”

Section: Wntsmentioning

confidence: 99%

Circular RNAs as potential regulators in bone remodeling: a narrative review

Pan¹,

Cen²,

Zhang³

et al. 2021

Ann Transl Med

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In this review, we focus on the recent progress of circular ribonucleic acids (circRNAs)-related molecular mechanisms in the processes of osteogenesis and osteoclastogenesis, and explore their roles in the development of bone-remodeling disorders.Background: The well-coupled bone-formation and bone-resorption processes are vital in bone remodeling. Once the balance is disrupted, bone-remodeling disorders (e.g., osteoporosis and osteopetrosis) occur, severely affecting patients' quality of life. CircRNAs, the newly discovered members of the noncoding RNA family, have been reported to act as key checkpoints of various signaling pathways that influence osteoblasts and osteoclasts functions, thus regulating the physiological and pathological processes of bone homeostasis.Methods: Three English and three Chinese databases [i.e., PubMed, Embase, MEDLINE (via Ovid), Chinese Biomedical Literature, China National Knowledge Infrastructure, and VIP databases] were searched to June 2021 without language restrictions. Studies exploring the roles of circRNAs in key bone remodeling mediators, such as Smad-dependent bone morphogenetic protein (BMP)/transforming growth factor beta (TGF-β), Wnts, runt-related transcription factor (RUNX), forkhead boxes (FOXs), colony-stimulating factor 1 (CSF-1), receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG), and circRNA-related bone-remodeling disorders, were included.Conclusions: Many circRNAs have been shown to promote osteogenesis and facilitate osteoclast differentiation via diverse mechanisms, and thus modulate the process of bone homeostasis. The imbalance or impairment of these two parts causes diseases, such as osteoporosis, and osteonecrosis of the femoral head, which are also closely correlated to the aberrant presence of circRNAs. Current evidence provides us with promising diagnosis and treatment methods for some bone homeostasis disorders.

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“…This ceRNA networking eliminates the regulatory and inhibitory effects of the miRNAs on their target genes and thus increasing the expression level of the target genes. It is widely accepted that CircRNA-miRNA network has a close relationship with osteogenic differentiation [ 18 ]. In a recent study, it was reported that Circ_0000020 promotes glioma cell growth, and links with poor prognosis [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ_0000020 promotes osteogenic differentiation to reduce osteoporosis via sponging microRNA miR-142-5p to up-regulate Bone Morphogenetic Protein BMP2

Zhou

Miao

et al. 2021

Bioengineered

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This study was designed to study functions of Circ_0000020 during osteogenic differentiation. First, we used RT-qPCR to detect the expression of Circ_0000020, miR-142-5p and osteogenesisrelated genes, whereas western blot analysis detected the expression of osteogenesis markers after the osteogenic differentiation of primary BMSCs isolated from rats. Alkaline phosphatase (ALP) activity and alizarin red Sstaining validated osteoblast phenotypes. Flow cytometry was used to detect cell apoptosis. Sh-Circ_0000020 was used to study the function of Circ_0000020 in osteogenic differentiation of BMSCs. Luciferase assay and RNA immunoprecipitation were used to validate the interaction between Circ_0000020 and miR-142-5p, and BMP2 and miR-142-5p. Cotransfection of miR-142-5p and sh-Circ_0000020 was used to verify the downstream signaling pathway. Circ_0000020 expression was up-regulated during osteogenic differentiation, whereas miR-142-5p expression was significantly decreased. Silencing Circ_0000020 inhibited osteogenic differentiation and promoted apoptosis, and inhibited ALP activity and mineralization ability. Moreover, Circ_0000020 interacts directly with miR-142-5p which binds to the BMP2 3 UTR and inhibits its expression. Additionally, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 rescued down-regulated BMP2, increased the expression osteogenesis-related gene expressions, and thereby rescued the inhibition of osteogenic differentiation induced by Circ_0000020 silencing. Furthermore, co-transfection of miR-142-5p inhibitors and sh-Circ_0000020 reversed Circ_0000020 silencing-induced downregulation of p-Smad1/5/8, Runx2, and Osterix protein levels. Circ_0000020 regulates BMP2 expression through sponging miR-142-5p as ceRNA, thereby positively regulating BMSCs osteogenic differentiation through Circ_0000020/miR-142-5p/BMP2/ SMAD-dependent signaling pathway.

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Dicalcium silicate microparticles modulate the differential expression of circRNAs and mRNAs in BMSCs and promote osteogenesis via circ_1983–miR-6931–Gas7 interaction

Abstract: Among C2S-induced differentially expressed circRNAs, circ_1983 is involved in osteogenesis via circ_1983–miR-6931–Gas7 ceRNA interaction-mediated Runx2 upregulation.

Cited by 19 publications

References 55 publications

Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

Circular RNAs as potential regulators in bone remodeling: a narrative review

Circular RNA circ_0000020 promotes osteogenic differentiation to reduce osteoporosis via sponging microRNA miR-142-5p to up-regulate Bone Morphogenetic Protein BMP2

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