Long noncoding RNA expression profiles during the NEL‐like 1 protein–induced osteogenic differentiation

Xia, Kai; Cen, Xiao; Yu, Liyuan; Huang, Xinqi; Sun, Weihao; Zhao, Zhihe; Liu, Jun

doi:10.1002/jcp.29526

Cited by 12 publications

(10 citation statements)

References 41 publications

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“…Ubiquitination and degradation of β-catenin are regulated by the balance of GSK-3β and p-GSK-3β [22]. β-Catenin interacts with TCF/LEF-1 or other transcription coactivators in the nucleus and induces the expression of osteogenesis-related molecules to regulate osteogenesis [24,25,47]. Compared with CON-ASCs, DOP-ASCs exhibited relatively downregulated expression of β-catenin, p-GSK-3β, RUNX2, and OPN.…”

Section: Discussionmentioning

confidence: 99%

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JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation

et al. 2021

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Background Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity. Methods The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree. Results Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression. Conclusions Intragenic DNA methylation inhibits the osteogenic ability of DOP-ASCs by suppressing expression of JKAMP and the Wnt signaling pathway. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs and provides a potential therapeutic target to prevent and treat osteoporosis.

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Section: Discussionmentioning

confidence: 99%

“…The Wnt signaling pathway is a highly conserved signaling pathway. Abnormal changes in Wnt signaling pathway markers are linked to changes in bone metabolism and the osteogenic ability of mesenchymal stem cells [23][24][25][26]. Recent study has shown that JNK1 is essential for osteoblast function in vivo and in vitro [27,28].…”

Section: Introductionmentioning

confidence: 99%

JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation

et al. 2021

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“…It was found that 323 lncRNAs were expressed differentially during osteogenesis and during NELL-1-induced osteogenesis. 114…”

Section: The Role Of Lncrnas In Osteogenesismentioning

confidence: 99%

LncRNAs as a new regulator of chronic musculoskeletal disorder

et al. 2021

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Musculoskeletal disorders are a group of conditions that affect the motor system, including bones, muscles, tendons, ligaments and joints. 1 People with multiple disorders are particularly vulnerable, especially in the context of an ageing population. Musculoskeletal disorders include a variety of conditions such as osteoarthritis (OA), rheumatoid arthritis (RA), osteopenia, osteoporosis, fractures, sarcopenia, etc. 2 Non-protein-coding RNA makes up 98% of the whole human genome. 3,4 These functional RNAs can be divided into two groups according to the threshold of 200 nucleotides (NTS): small and long non-coding RNAs (lncRNAs). 5,6 LncRNAs regulate the activities of both nearby and distant genes by multiple mechanisms. It could act as a scaffold for transcription factors and other molecules involved in transcription initiation. 7 Moreover, it could serve as protein and microRNA decoys to interfere with cell division by regulating a series of key genes. 8 For those mainly located in the cytoplasm, it could directly target mRNA and induce translation. 9 Currently, an increased number of lncRNAs are found to be involved in the regulation of development and homeostasis of skeletal muscle system. 10,11 It is notable that lncRNAs take key roles in musculoskeletal disorders.

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“…Long noncoding RNAs (lncRNAs) are defined as a set of noncoding RNAs longer than 200bp that have no protein-coding ability. Evidence is rapidly accumulating on the functions of lncRNAs in epigenetic regulation in the differentiation of MSCs and the occurrence of many diseases[ 18 - 21 ]. In this review, we revisit the epigenetic regulatory mechanisms of lncRNAs involved in DNA methylation and histone modifications and summarize the biological functions of lncRNAs in regulation crucial differentiation- and bone disease-related genes by interacting with key epigenetic modifiers.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Xia¹,

Yu²,

Huang³

et al. 2022

WJSC

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Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis, which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells (MSCs). Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases, including osteoporosis and osteoarthritis. In addition to conventional genetic modifications, epigenetic modifications ( i.e. , DNA methylation, histone modifications, and the expression of noncoding RNAs) are considered to be contributing factors that affect bone homeostasis. Long noncoding RNAs (lncRNAs) were previously regarded as ‘transcriptional noise’ with no biological functions. However, substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases. In this review, we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

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Long noncoding RNA expression profiles during the NEL‐like 1 protein–induced osteogenic differentiation

Cited by 12 publications

References 41 publications

JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation

JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation

LncRNAs as a new regulator of chronic musculoskeletal disorder

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

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