Transcriptome dynamics of long noncoding RNAs and transcription factors demarcate human neonatal, adult, and human mesenchymal stem cell-derived engineered cartilage.

Autor:	Vail DJ; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH., Somoza RA; Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH., Caplan AI; Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH., Khalil AM; Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.
Jazyk:	angličtina
Zdroj:	Journal of tissue engineering and regenerative medicine [J Tissue Eng Regen Med] 2020 Jan; Vol. 14 (1), pp. 29-44. Date of Electronic Publication: 2019 Dec 18.
DOI:	10.1002/term.2961
Abstrakt:	The engineering of a native-like articular cartilage (AC) is a long-standing objective that could serve the clinical needs of millions of patients suffering from osteoarthritis and cartilage injury. An incomplete understanding of the developmental stages of AC has contributed to limited success in this endeavor. Using next generation RNA sequencing, we have transcriptionally characterized two critical stages of AC development in humans-that is, immature neonatal and mature adult, as well as tissue-engineered cartilage derived from culture expanded human mesenchymal stem cells. We identified key transcription factors (TFs) and long noncoding RNAs (lncRNAs) as candidate drivers of the distinct phenotypes of these tissues. AGTR2, SCGB3A1, TFCP2L1, RORC, and TBX4 stand out as key TFs, whose expression may be capable of reprogramming engineered cartilage into a more expandable and neonatal-like cartilage primed for maturation into biomechanically competent cartilage. We also identified that the transcriptional profiles of many annotated but poorly studied lncRNAs were dramatically different between these cartilages, indicating that lncRNAs may also be playing significant roles in cartilage biology. Key neonatal-specific lncRNAs identified include AC092818.1, AC099560.1, and KC877982. Collectively, our results suggest that tissue-engineered cartilage can be optimized for future clinical applications by the specific expression of TFs and lncRNAs. (© 2019 John Wiley & Sons, Ltd.)
Databáze:	MEDLINE
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