Age-related differential gene and protein expression in postnatal cartilage canal and osteochondral junction chondrocytes

Duesterdieck-Zellmer, Katja F.; Semevolos, Stacy A.; Kinsley, Marc A.; Riddick, Tara L.

doi:10.1016/j.gep.2014.11.002

Cited by 15 publications

(18 citation statements)

References 46 publications

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“…The cellular targets of Hh ligands in the liver are somewhat uncertain because it appears that the Hh-responsiveness of liver-resident cells is influenced by various factors, including circadian periodicity, age, and health (Borjigin et al, 1999; Duesterdieck-Zellmer et al, 2015). Mature hepatocytes in healthy adult livers are believed to be Hh unresponsive (Sicklick et al, 2006) because they do not have a PC (Wheatley, Wang, and Strugnell, 1996).…”

Section: Physiology Of the Hedgehog Pathway In The Livermentioning

confidence: 99%

The hedgehog pathway in nonalcoholic fatty liver disease

Machado

Diehl

2018

Critical Reviews in Biochemistry and Molecular Biology

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Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high prevalence of obesity-related fatty liver (hepatic steatosis) and the lack of specific treatments to prevent hepatic steatosis from progressing to more serious forms of liver damage, including nonalcoholic steatohepatitis (NASH), cirrhosis, and primary liver cancer. The pathogenesis of NAFLD is complex, and not fully understood. However, compelling evidence demonstrates that dysregulation of the hedgehog (Hh) pathway is involved in both the pathogenesis of hepatic steatosis and the progression from hepatic steatosis to more serious forms of liver damage. Inhibiting Hedgehog signaling enhances hepatic steatosis, a condition which seldom results in liver-related morbidity or mortality. In contrast, excessive Hedgehog pathway activation promotes development of NASH, cirrhosis, and primary liver cancer, the major causes of liver-related deaths. Thus, suppressing excessive Hh pathway activity is a potential approach to prevent progressive liver damage in NAFLD. Various pharmacologic agents that inhibit Hh signaling are available and approved for cancer therapeutics; more are being developed to optimize the benefits and minimize the risks of inhibiting this pathway. In this review we will describe the Hh pathway, summarize the evidence for its role in NAFLD evolution, and discuss the potential role for Hh pathway inhibitors as therapies to prevent NASH, cirrhosis and liver cancer.

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Section: Physiology Of the Hedgehog Pathway In The Livermentioning

confidence: 99%

The hedgehog pathway in nonalcoholic fatty liver disease

Machado

Diehl

2018

Critical Reviews in Biochemistry and Molecular Biology

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“…We found that HOTAIR over-expression in SW1353 cells matched the expression pro le of OA-related genes in human primary osteoarthritic chondrocytes, The roles of WIF-1 in skeletal tissue development has been investigated in other studies. WIF-1 is shown to be a multifunctional modulator of signalling pathways in cartilage development (46,47), and has differential expression during neonatal and pre-adolescent development in chondrocytes surrounding cartilage canals and the osteochondral junction (48). Moreover, WIF-1 is shown to have a protective effect against cartilage degradation in experimental arthritis, and has important effects in promoting the balance of cartilage and bone turnover (49).…”

Section: Discussionmentioning

confidence: 99%

A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway

Yang

Xing

Wang

et al. 2020

Preprint

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Abstract Background: Long noncoding RNAs (lncRNAs) are recently found to be critical regulators of the epigenome. However, our knowledge of their role in osteoarthritis (OA) development is limited. This study investigates the mechanism by which HOTAIR, a key lncRNA with elevated expression in OA, affects OA disease progression.Results: HOTAIR expression was greatly elevated in osteoarthritic compared to normal chondrocytes. Silencing and over-expression of HOTAIR in SW1353 cells respectively reduced and increased the expression of genes associated with cartilage degradation in OA. Investigation of molecular pathways revealed that HOTAIR acted directly on Wnt inhibitory factor 1 (WIF-1) by increasing histone H3K27 trimethylation in the WIF-1 promoter, leading to WIF-1 repression that favours activation of the Wnt/β-catenin pathway.Conclusions: Activation of Wnt/β-catenin signalling by HOTAIR through WIF-1 repression in osteoarthritic chondrocytes increases catabolic gene expression and promotes cartilage degradation. This is the first study to demonstrate a direct link between HOTAIR, WIF-1 and OA progression, which may be useful for future investigations into disease biomarkers or therapeutic targets.

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“…Among these, the highest levels of expression were in S FRP5 and SCGB3A1 . SFRP5 is a WNT signaling inhibitor of the secreted frizzled‐related protein family and has been shown to be expressed at low levels in the deep zone of neonatal mouse cartilage by E15.5 (Lui et al, ; Witte, Dokas, Neuendorf, Mundlos, & Stricker, ) as well as in equine neonatal AC (Duesterdieck‐Zellmer, Semevolos, Kinsley, & Riddick, ). Given the importance of WNT signaling in limb bud and cartilage development and the dramatic differences in expression between adult and neonatal AC, SFRP5 stands out as a key candidate molecular driver of human neonatal AC phenotypes.…”

Section: Discussionmentioning

confidence: 99%

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

Vail

Somoza

Caplan

et al. 2019

J Tissue Eng Regen Med

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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.

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Age-related differential gene and protein expression in postnatal cartilage canal and osteochondral junction chondrocytes

Cited by 15 publications

References 46 publications

The hedgehog pathway in nonalcoholic fatty liver disease

The hedgehog pathway in nonalcoholic fatty liver disease

A long non-coding RNA, HOTAIR, promotes cartilage degradation in osteoarthritis by inhibiting WIF-1 expression and activating Wnt pathway

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

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