Assessment of the profiling MicroRNA expression of differentiated and dedifferentiated human adult articular chondrocytes

Abstract

MicroRNA has an important role in regulating gene expression during cell differentiation. In this study we identified the expression pattern of microRNA in the differentiated and dedifferentiated chondrocytes. Adult human articular chondrocytes were cultured in monolayer. RNA was isolated from the differentiated chondrocytes (collected after isolation) and the fifth-passage (dedifferentiated) chondrocytes, and subjected to gene expression analysis using microRNA and cDNA microarray analysis. Real-time RT-PCR was also performed to confirm the differentially expressed genes. Furthermore, we integrated microRNA and cDNA microarray data together with computational approaches, such as microRNA gene target prediction algorithms, to reveal the role of microRNAs involved in chondrocyte homeostasis. The results showed a dramatic change in expression of microRNA between the two cell types. Thirteen upregulated and 12 down-regulated microRNAs were detected in differentiated chondroctes. We also revealed microRNA-gene target pairs potentially involved in dedifferentiation process. Our results revealed novel findings of differential expression of microRNA in dedifferentiation, and microRNA could have an important role in the maintenance of chondrocytes homeostasis. MicroRNA may be a target for cartilage tissue engineering and regenerative medicine. ß

MicroRNA‐199a‐3p, microRNA‐193b, and microRNA‐320c are correlated to aging and regulate human cartilage metabolism

“…In miRNA expression analysis on differentiated and dedifferentiated chondrocytes, miR-193b expression is about 7.6-fold higher in dedifferentiated chondrocytes than in differentiated chondrocytes (Table 5). 22 However, there is no report on the functional analysis of miR-193b. Our study is the first report that miR-193b affects human cartilage metabolism by regulating type 2 collagen, aggrecan, and SOX9 expression.…”

“…MiR199a-3p and miR-193b may be involved in cartilage degeneration, and we found nothing that contradicts previous reports. 21,22 ADAMTS5 is an efficient aggrecanase and induces cartilage degeneration. Although miR-320c has not been reported in relation to cartilage, the expression of ADAMTS5 was downregulated in the miR-320c mimic group and was upregulated in the inhibitor group.…”

Epigenomic and microRNA-mediated regulation in cartilage development, homeostasis, and osteoarthritis

“…Although the OA expression status of miR-675 and its target remain unknown, these data indicate that miR-675 may modulate cartilage homeostasis by suppressing a COL2A1 transcriptional repressor [85]. Profiling studies of primary adult articular chondrocytes show that miRNAs are differentially expressed in cells with a range of differentiated, chondroblast-like, and dedifferentiated phenotypes, suggesting that manipulating miRNA profiles may provide new strategies for improving cartilage tissue engineering [86, 87]. …”

Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum

“…It is established that dedifferentiation is necessary to achieve a high cell number, and it is considered a curative step in such technologies [28-30]. However, massive dedifferentiation of chondrocytes results in loss of the chondrogenic phenotype and formation of primitive multipotent cell types [28-31]. To overcome such shortcomings, chondrogenic maintenance cues such as cytokines, chemokines, and growth factors are required to regulate and control the process of chondrocyte transplantation.…”