Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648

Zhang, Min; Liu, Xiaomeng; Li, Zheng; Du, Yangge; Liu, Xuejiao; Lv, Longwei; Zhang, Xiao; Liu, Yunsong; Zhang, Ping; Zhou, Yongsheng

doi:10.1038/s41419-019-1815-7

Cited by 45 publications

(25 citation statements)

References 64 publications

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“…The Peking University Animal Care and Use Committee approved the in vivo study (LA2019019). The in vivo study was conducted as previously described [31]. For 7 days before the implantation study, hASCs infected with lentivirus harboring shNC, shLAP2α-1, and shLAP2α-2 were induced into osteoblasts.…”

Section: Heterotopic Bone Formation In Vivomentioning

confidence: 99%

Knockdown of LAP2α inhibits osteogenic differentiation of human adipose-derived stem cells by activating NF-κB

Tang

Zhang

et al. 2020

Stem Cell Res Ther

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Background: Lamina-associated polypeptide 2α (LAP2α) is a nucleoplasmic protein that has been involved in the regulation of the cell cycle, gene transcription, and adult stem cell function. LAP2α down-regulation is linked to age-related osteoporosis and bone deformities; however, the underlying mechanisms remain obscure. The present study aimed to elucidate the function of LAP2α in the osteogenic differentiation of human adipose-derived stem cells (hASCs), which are attractive sources for bone tissue engineering. Methods: The expression of LAP2α during the osteogenic differentiation of hASCs was detected firstly. A loss of function investigation was then carried out to characterize the function of LAP2α in osteogenic differentiation of hASCs both in vitro and in vivo. Moreover, RNA-sequences, western blotting, and confocal analyses were performed to clarify the molecular mechanism of LAP2α-regulated osteogenesis. Results: We found that LAP2α expression was upregulated upon osteogenic induction. Both in vitro and in vivo experiments indicated that LAP2α knockdown resulted in impaired osteogenic differentiation of hASCs. Mechanistically, we revealed that LAP2α deficiency activated nuclear factor kappa B (NF-κB) signaling by controlling the cytoplasmic-nuclear translocation of p65. Conclusions: Collectively, our findings revealed that LAP2α functions as an essential regulator for osteogenesis of hASCs by modulating NF-κB signaling, thus providing novel insights for mesenchymal stem cell-mediated bone tissue engineering.

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Section: Heterotopic Bone Formation In Vivomentioning

confidence: 99%

Knockdown of LAP2α inhibits osteogenic differentiation of human adipose-derived stem cells by activating NF-κB

Tang

Zhang

et al. 2020

Stem Cell Res Ther

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“…PCK2 was a potential target for osteoporosis treatment Ovariectomized (OVX) mice are typically used as an osteoporotic model to induce bone loss and aging mice ( 12-month old) are generally known as the model of impaired bone formation [26,29]. To investigate the possible functional signi cance of PCK2 in bone remodeling in vivo, we rst established OVX mice and aged mice (18-month old, 18m) to examine the PCK2 status in osteoporotic mice BMMSCs.…”

Section: Resultsmentioning

confidence: 99%

“…1b-d). Next, BMMSCs were isolated from mouse bone marrow by the traditional flush method [26]. As shown in additional le 4: Figure.…”

Section: Resultsmentioning

confidence: 99%

“…Puri ed PCK2 overexpression lentivirus (PCK2 lentivirus, Vector Builder Co., Guangzhou, China) was used to overexpress PCK2 in vivo. Puri ed PCK2 lentivirus (1×10 9 GC) or control virus (vector, 1×10 9 GC) were tail-injected into the SHAM/OVX/6-week/18-mouth mice twice a week for up to 4 weeks [25,26]. After the four-week treatment, mice were sacri ced immediately for histological assessments and BMMSCs isolation.…”

Section: Establishment Of Estrogen De Ciency-induced Osteoporosis Micementioning

confidence: 99%

“…The bone marrow was ushed out of mouse femurs and harvested as previously reported in our work [26]. After centrifugation for 5min at 1200rpm, the cells were collected and cultured in fresh α-MEM mixed with 20% FBS and 1% antibiotics.…”

Section: Isolation Of Primary Mbmmscsmentioning

confidence: 99%

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Mitochondrial Phosphoenolpyruvate Carboxykinase (PCK2) Maintains the Function of Bone Marrow Mesenchymal Stromal/stem Cells to Rescue Osteoporotic Phenotype Partly Through Autophagy Dependent Manner

Li¹,

Liu²,

Liu³

et al. 2020

Preprint

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BackgroundMitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a rate-limiting enzyme that plays critical roles in multiple physiological processes. We unveiled the important role of PCK2 on the regulation of osteogenesis by mesenchymal stromal/stem cells (MSCs) in our previous work. Here we further investigated the roles of PCK2 on regulating adipogenesis of MSCs and its therapeutic effect on osteoporosis. MethodsWe investigated PCK2 function in adipogenic differentiation of MSCs in vitro through loss-and-gain-of-function experiments. This was followed by heterotopic adipose formation assay in nude mice. In addition, ovariectomized (OVX) and aged mice were used as osteoporotic models to test the effect of PCK2 on osteoporosis. The bone formation and adipocyte accumulation were assessed by micro-CT and histological analysis. The multipotent capacity of control and osteoporotic BMMSCs were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot analysis. ResultsPCK2 expression levels were signiﬁcantly decreased in BMMSCs from OVX and aged mice. Furthermore, PCK2 could inhibit adipogenesis of BMMSCs and thus resisting lipid droplet formation and attenuating bone loss in osteoporotic mice. Mechanistically, we detected that autophagy level was decreased in BMMSCs of osteoporotic mice, while overexpression of PCK2 in vivo could rescued the autophagy activity. We further indicated that PCK2 could reverse osteopenia phenotype and adipose formation in OVX and aged mice partially via autophagy.ConclusionsCollectively, we suggested that PCK2 could attenuate bone loss and adipocyte accumulation of BMMSCs in osteoporotic mice through autophagy dependent manner. Our study indicated that PCK2 could be a brand and effective therapeutic target for osteoporosis treatment.

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The evolution of de novo human‐specific microRNA genes on chromosome 21

Johnson

Blandino

Mercado

et al. 2022

American Journal of Biological Anthropology

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The genetic basis of human uniqueness remains one of the most enduring mysteries in biological anthropology. The goal of this research project was to identify, characterize, and infer the origin and function of novel elements in the human genome that are not functionally shared with other apes. Our approach toward this goal was to utilize a variety of genome alignment tools to discover islands of non‐conserved DNA sequences, followed by theoretical and computational analysis of those regions using synteny sequence analysis. We discovered families of microRNA genes on human chromosome 21 with no detectable orthologs in the other African apes. We then developed a working model of their origin through repeated rounds of segmental duplication occurring within an array of rRNA genes. Target prediction reveals potential roles for these microRNA genes in the embryonic development of the central nervous system. We conclude that the 21p11 region of human chromosome 21 has undergone segmental duplication events that generated de novo microRNA genes from within a field of rRNA genes. These microRNA genes may have played a role in the unique evolutionary trajectory of the human lineage through their modulation of genes involved in embryonic development.

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Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648

Cited by 45 publications

References 64 publications

Knockdown of LAP2α inhibits osteogenic differentiation of human adipose-derived stem cells by activating NF-κB

Knockdown of LAP2α inhibits osteogenic differentiation of human adipose-derived stem cells by activating NF-κB

Mitochondrial Phosphoenolpyruvate Carboxykinase (PCK2) Maintains the Function of Bone Marrow Mesenchymal Stromal/stem Cells to Rescue Osteoporotic Phenotype Partly Through Autophagy Dependent Manner

The evolution of de novo human‐specific microRNA genes on chromosome 21

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