MicroRNAs regulating TGFβ and BMP signaling in the osteoblast lineage

Garcia, John; Delany, Anne M.

doi:10.1016/j.bone.2020.115791

Cited by 26 publications

(27 citation statements)

References 83 publications

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“…BMP2 and Wnt3a regulate osteoblast differentiation and bone formation [40][41][42]. BMP2 activates Smad1/5/8 proteins by binding to BMP receptors, induces the translocation of Smad1/5/8 proteins from the cytosol to the nucleus, and then Smad1/5/8 and Smad4 complexes regulate gene transcription in the nucleus [43].…”

Section: Discussionmentioning

confidence: 99%

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Park

Lee

Cho

et al. 2021

IJMS

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Paeonia suffruticosa is a magnificent and long-lived woody plant that has traditionally been used to treat various diseases including inflammatory, neurological, cancer, and cardiovascular diseases. In the present study, we demonstrated the biological mechanisms of paeonoside (PASI) isolated from the dried roots of P. suffruticosa in pre-osteoblasts. Herein, we found that PASI has no cytotoxic effects on pre-osteoblasts. Migration assay showed that PASI promoted wound healing and transmigration in osteoblast differentiation. PASI increased early osteoblast differentiation and mineralized nodule formation. In addition, PASI enhanced the expression of Wnt3a and bone morphogenetic protein 2 (BMP2) and activated their downstream molecules, Smad1/5/8 and β-catenin, leading to increases in runt-related transcription factor 2 (RUNX2) expression during osteoblast differentiation. Furthermore, PASI-mediated osteoblast differentiation was attenuated by inhibiting the BMP2 and Wnt3a pathways, which was accompanied by reduction in the expression of RUNX2 in the nucleus. Taken together, our findings provide evidence that PASI enhances osteoblast differentiation and mineralized nodules by regulating RUNX2 expression through the BMP2 and Wnt3a pathways, suggesting a potential role for PASI targeting osteoblasts to treat bone diseases including osteoporosis and periodontitis.

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Section: Discussionmentioning

confidence: 99%

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Park

Lee

Cho

et al. 2021

IJMS

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“…osteoblasts, which are derived from multipotent mesenchymal stem cells, have an important function in maintaining bone microstructure and homeostasis, and the dysregulation of oB number or activity is related to the pathophysiology of bone disorders, such as osteoporosis (88). numerous studies have revealed that mirnas, lncrnas and circrnas are crucial factors involved in oB proliferation, differentiation, autophagy and apoptosis in osteogenesis.…”

Section: Mechanisms By Which Ncrnas Regulate Obs In Osteoporosismentioning

confidence: 99%

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

Han

Tan

et al. 2021

Mol Med Rep

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osteoporosis is a common metabolic bone disorder typically characterized by decreased bone mass and an increased risk of fracture. at present, the detailed molecular mechanism underlying the development of osteoporosis remains to be elucidated. accumulating evidence shows that non-coding (nc)rnas, such as micrornas (mirnas), long ncrnas (lncrnas) and circular rnas (circRNAs), play significant roles in osteoporosis through the post-transcriptional regulation of gene expression as regulatory factors. Previous studies have demonstrated that ncrnas participate in maintaining bone homeostasis by regulating physiological and developmental processes in osteoblasts, osteoclasts and bone marrow stromal cells. in the present review, the latest research investigating the involvement of mirnas, lncrnas and circrnas in regulating the differentiation, proliferation, apoptosis and autophagy of cells that maintain the bone microenvironment in osteoporosis is summarized. deeper insight into the aspects of osteoporosis pathogenesis involving the deregulation of ncrnas could facilitate the development of therapeutic approaches for osteoporosis. Contents 1. introduction 2. Mechanisms by which ncrnas regulate BMScs in osteoporosis 3. Mechanisms by which ncrnas regulate oBs in osteoporosis 4. Mechanisms by which ncrnas regulate ocs in osteoporosis 5. conclusion and perspectives

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“…In the last decade, microRNA (miRNA)-mediated mechanisms have emerged as key to the regulation of bone resorption and formation. (10)(11)(12)(13)(14) miRNAs are small noncoding RNAs that exert their regulatory role through direct interaction with messenger RNAs (mRNAs). When loaded into the RNA-induced silencing complex (RISC), miRNAs act as a "guiding strand" to recruit the RISC to complementary regions within target mRNAs.…”

Section: Introductionmentioning

confidence: 99%

“…(15)(16)(17) In the mesenchymal lineage, miRNAs can promote or inhibit differentiation toward the osteoblastic fate through modulation of signaling pathways important in bone formation, including the Wnt, transforming growth factor β (TGFβ), and bone morphogenetic protein (BMP) pathways. (10)(11)(12)(18)(19)(20)(21)(22) A single miRNA can potentially target many distinct mRNAs. Frequently, miRNAs target multiple mRNAs involved in the same or correlated pathways, to modify the tempo and amplitude of signaling programs, suggesting that miRNAs could be excellent targets for therapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

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miR-433-3p suppresses bone formation and mRNAs critical for osteoblast function in mice

Garcia

Smith

Karki

et al. 2020

Journal of Bone and Mineral Research

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MicroRNAs (miRNAs) are key posttranscriptional regulators of osteoblastic commitment and differentiation. miR-433-3p was previously shown to target Runt-related transcription factor 2 (Runx2) and to be repressed by bone morphogenetic protein (BMP) signaling. Here, we show that miR-433-3p is progressively decreased during osteoblastic differentiation of primary mouse bone marrow stromal cells in vitro, and we confirm its negative regulation of this process. Although repressors of osteoblastic differentiation often promote adipogenesis, inhibition of miR-433-3p did not affect adipocyte differentiation in vitro. Multiple pathways regulate osteogenesis. Using luciferase-3 0 untranslated region (UTR) reporter assays, five novel miR-433-3p targets involved in parathyroid hormone (PTH), mitogen-activated protein kinase (MAPK), Wnt, and glucocorticoid signaling pathways were validated. We show that Creb1 is a miR-433-3p target, and this transcription factor mediates key signaling downstream of PTH receptor activation. We also show that miR-433-3p targets hydroxysteroid 11-β dehydrogenase 1 (Hsd11b1), the enzyme that locally converts inactive glucocorticoids to their active form. miR-433-3p dampens glucocorticoid signaling, and targeting of Hsd11b1 could contribute to this phenomenon. Moreover, miR-433-3p targets R-spondin 3 (Rspo3), a leucine-rich repeat-containing G-protein coupled receptor (LGR) ligand that enhances Wnt signaling. Notably, Wnt canonical signaling is also blunted by miR-433-3p activity. In vivo, expression of a miR-433-3p inhibitor or tough decoy in the osteoblastic lineage increased trabecular bone volume. Mice expressing the miR-433-3p tough decoy displayed increased bone formation without alterations in osteoblast or osteoclast numbers or surface, indicating that miR-433-3p decreases osteoblast activity. Overall, we showed that miR-433-3p is a negative regulator of bone formation in vivo, targeting key bone-anabolic pathways including those involved in PTH signaling, Wnt, and endogenous glucocorticoids. Local delivery of miR-433-3p inhibitor could present a strategy for the management of bone loss disorders and bone defect repair.

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MicroRNAs regulating TGFβ and BMP signaling in the osteoblast lineage

Cited by 26 publications

References 83 publications

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

miR-433-3p suppresses bone formation and mRNAs critical for osteoblast function in mice

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