Notch-RBPJ Pathway for the Differentiation of Bone Marrow Mesenchymal Stem Cells in Femoral Head Necrosis

Liu, Kangping; Ge, Hongfan; Liu, Chengyin; Jiang, Yixin; Yu, Yaling; Zhou, Zhenlei

doi:10.3390/ijms24076295

Cited by 3 publications

(1 citation statement)

References 49 publications

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“…The notch signaling pathway regulates cell functions, such as proliferation, differentiation, and cell-fate decisions. Notch reception activation may produce γ-secretase-cleaved NICD, which is translocated into the nucleus for the transcriptional regulation of target genes, such as HES [76]. The importance of notch signaling in bone formation has been demonstrated [77].…”

Section: The Underlying Mechanisms Of Naringin In Protecting Against ...mentioning

confidence: 99%

The Development of Naringin for Use against Bone and Cartilage Disorders

Gan

Deng

et al. 2023

Molecules

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Bone and cartilage disorders are the leading causes of musculoskeletal disability. There is no absolute cure for all bone and cartilage disorders. The exploration of natural compounds for the potential therapeutic use against bone and cartilage disorders is proving promising. Among these natural chemicals, naringin, a flavanone glycoside, is a potential candidate due to its multifaceted pharmacological activities in bone and cartilage tissues. Emerging studies indicate that naringin may promote osteogenic differentiation, inhibit osteoclast formation, and exhibit protective effects against osteoporosis in vivo and in vitro. Many signaling pathways, such as BMP-2, Wnt/β-catenin, and VEGF/VEGFR, participate in the biological actions of naringin in mediating the pathological development of osteoporosis. In addition, the anti-inflammatory, anti-oxidative stress, and anti-apoptosis abilities of naringin also demonstrate its beneficial effects against bone and cartilage disorders, including intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, bone and cartilage tumors, and tibial dyschondroplasia. Naringin exhibits protective effects against bone and cartilage disorders. However, more efforts are still needed due to, at least in part, the uncertainty of drug targets. Further biological and pharmacological evaluations of naringin and its applications in bone tissue engineering, particularly its therapeutic effects against osteoporosis, might result in developing potential drug candidates.

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Section: The Underlying Mechanisms Of Naringin In Protecting Against ...mentioning

confidence: 99%

The Development of Naringin for Use against Bone and Cartilage Disorders

Gan

Deng

et al. 2023

Molecules

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USP13 overexpression in BMSCs enhances anti-apoptotic ability and guards against methylprednisolone-induced osteonecrosis in rats

Jiang,

Fan,

et al. 2024

Stem Cells

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Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pre-treatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.

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Tanshinone IIA promotes osteogenic differentiation potential and suppresses adipogenic differentiation potential of bone marrow mesenchymal stem cells

Wang,

Wu,

Feng

et al. 2024

Mol Med Rep

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Tanshinone IIA (Tan IIA) may have therapeutic effects on avascular necrosis of the femoral head (ANFH) by targeting bone marrow mesenchymal stem cells (BMSCs). The effect and underlying mechanism of Tan IIA on adipogenesis and osteogenesis ability of BMSCs remain to be elucidated. In the present study BMSCs were treated with osteogenic or adipogenic differentiation medium with or without Tan IIA under hypoxic environment. Osteogenic differentiation potential was evaluated by alkaline phosphatase (ALP) measurement, alizarin red staining and reverse transcription-quantitative (RT-q) PCR of osteogenic marker genes. Adipogenic differentiation potential was evaluated with oil red staining and RT-qPCR of adipogenic marker genes. Detailed mechanism was explored by RNA-seq and small molecular treatment during osteogenesis and adipogenesis of BMSCs. ALP level, mineralized nodules and expression level of osteogenic marker genes significantly increased following Tan IIA treatment during osteogenic differentiation of BMSCs. Lipid droplet and expression levels of adipogenic marker genes significantly decreased following Tan IIA treatment during adipogenic differentiation of BMSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of RNA-seq data indicated increased Akt and TGFβ signaling following Tan IIA treatment. Further western blot assay confirmed that Tan IIA significantly activated Akt/cAMP response element-binding protein signaling and TGFβ/Smad3 signaling. Application of Akti1/2 (an Akt inhibitor) significantly decreased the promotion effect of osteogenesis induced by Tan IIA, while the addition of SB431542 significantly reduced inhibition effect of adipogenesis caused by Tan IIA. Tan IIA could promote osteogenic differentiation potential of BMSCs by activating AKT signaling and suppress adipogenic differentiation potential of BMSCs by activating TGFβ signaling.

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Notch-RBPJ Pathway for the Differentiation of Bone Marrow Mesenchymal Stem Cells in Femoral Head Necrosis

Cited by 3 publications

References 49 publications

The Development of Naringin for Use against Bone and Cartilage Disorders

The Development of Naringin for Use against Bone and Cartilage Disorders

USP13 overexpression in BMSCs enhances anti-apoptotic ability and guards against methylprednisolone-induced osteonecrosis in rats

Tanshinone IIA promotes osteogenic differentiation potential and suppresses adipogenic differentiation potential of bone marrow mesenchymal stem cells

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