Inactivation of Ihh in Sp7-Expressing Cells Inhibits Osteoblast Proliferation, Differentiation, and Bone Formation, Resulting in a Dwarfism Phenotype with Severe Skeletal Dysplasia in Mice

Wang, Yunfei; Dong, Zhengquan; Yang, Ruijia; Zong, Sujing; Wei, Xiaochun; Wang, Chunfang; Guo, Li; Sun, Jian; Li, Haoqian; Li, Pengcui

doi:10.1007/s00223-022-00999-5

Cited by 6 publications

(2 citation statements)

References 40 publications

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“…Consistently, this study also demonstrated that rhBMP2 increases the levels of p-Smad1/5 and Runx2, thereby significantly reversing the inhibitory effects of miR-93-5p and miR-374a-5p on calcification and osteogenic differentiation of hAVICs by directly targeting BMP2/Smad1/5/Runx2 pathway. The regulation of Runx2 by different miRNAs in relation to osteogenic differentiation has been shown in previous studies, 43–45 including the authors' own one. 46 These results confirmed that miR-93-5p and miR-374a-5p may inhibit hAVICs calcification and osteogenic differentiation that associated with calcium and phosphorus dysmetabolism by inhibiting the BMP2/Smad1/5/Runx2 signaling pathway.…”

Section: Discussionsupporting

confidence: 58%

Overexpression of microRNA-93-5p and microRNA-374a-5p suppresses the osteogenic differentiation and mineralization of human aortic valvular interstitial cells via the BMP2/Smad1/5/RUNX2 signaling pathway

Liu

Zhang

Guo

et al. 2023

Journal of Cardiovascular Pharmacology

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Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate–induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium–phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.

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Section: Discussionsupporting

confidence: 58%

Overexpression of microRNA-93-5p and microRNA-374a-5p suppresses the osteogenic differentiation and mineralization of human aortic valvular interstitial cells via the BMP2/Smad1/5/RUNX2 signaling pathway

Liu

Zhang

Guo

et al. 2023

Journal of Cardiovascular Pharmacology

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“…Indian hedgehog (IHH) is a member of the hedgehog family, and it regulates the actions of tissue patterning, skeletogenesis, and cell proliferation. A deficiency of IHH may inhibit osteoblast development [84]. Naringin can upregulate the expression of Foxc2 and promote osteogenic differentiation in BMSCs.…”

Section: Potential Applications Of Naringin In Bone Tissue Engineeringmentioning

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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Hsa-miR-15b-5p/miR-195-5p Controls Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells Through Regulating Indian Hedgehog Expression

Harimi,

Khansarinejad,

Fesahat

et al. 2023

Appl Biochem Biotechnol

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Inactivation of Ihh in Sp7-Expressing Cells Inhibits Osteoblast Proliferation, Differentiation, and Bone Formation, Resulting in a Dwarfism Phenotype with Severe Skeletal Dysplasia in Mice

Cited by 6 publications

References 40 publications

Overexpression of microRNA-93-5p and microRNA-374a-5p suppresses the osteogenic differentiation and mineralization of human aortic valvular interstitial cells via the BMP2/Smad1/5/RUNX2 signaling pathway

Overexpression of microRNA-93-5p and microRNA-374a-5p suppresses the osteogenic differentiation and mineralization of human aortic valvular interstitial cells via the BMP2/Smad1/5/RUNX2 signaling pathway

The Development of Naringin for Use against Bone and Cartilage Disorders

Hsa-miR-15b-5p/miR-195-5p Controls Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells Through Regulating Indian Hedgehog Expression

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