Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation

Asmussen, Niels C; Zhao, Lin; McClure, Michael J.; Schwartz, Zvi; Boyan, Barbara D.

doi:10.1016/j.steroids.2017.12.003

Cited by 12 publications

(8 citation statements)

References 49 publications

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“…Vitamin D3 acts as an immune regulator and a stimulator of neurotrophic factors and neurotransmitter expression ( Jo et al., 2015 ). Chondrocytes can produce vitamin D metabolites under the regulation of growth factors and hormones, and these metabolites play an important role in the regulation of matrix vesicles ( Assmusen et al., 2017 ). Vitamin D3 has been suggested to dampen OA, which may indicate a relationship between vitamin D3 and OA ( Hansen et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes

Hanssoń

Skiöldebrand

2021

Current Research in Pharmacology and Drug Discovery

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Aims To treat osteoarthritic chondrocytes and thereby reduce the inflammation with a drug combination that primarily affects 5-HT- and ATP-evoked Ca 2+ signaling. In osteoarthritic chondrocytes, Ca 2+ signaling is elevated, resulting in increased production of ATP and inflammatory mediators. The expression of TLR4 and Na + /K + -ATPase was used to evaluate the inflammatory status of the cells. Main methods Equine chondrocytes were collected from joints with mild structural osteoarthritic changes and cultured in monolayers. The cells were treated with a combination of bupivacaine (1 pM) and sildenafil (1 μM) in combination with vitamin D3 (100 nM). A high-throughput screening system, the Flexstation 3 microplate reader, was used to measure intra- and extracellular Ca 2+ signaling after exposure to 5-HT, glutamate, or ATP. Expression of inflammatory receptors was assessed by Western blotting. Key findings Drug treatment substantially reduced 5-HT- and ATP-evoked intracellular Ca 2+ release and TLR4 expression compared to those in untreated chondrocytes. The combination of sildenafil, vitamin D3 together with metformin, as the ability to take up glucose is limited, increased Na + /K + -ATPase expression. Significance The combination of these three therapeutic substances at concentrations much lower than usually used, reduced expression of the inflammatory receptor TLR4 and increased the cell membrane enzyme Na + /K + -ATPase, which regulates cell volume and reduces increased intracellular Ca 2+ concentrations. These remarkable results indicate that this drug combination has disease-modifying osteoarthritis drug (DMOAD) properties and may be a new clinical therapy for osteoarthritis (OA).

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Section: Discussionmentioning

confidence: 99%

Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes

Hanssoń

Skiöldebrand

2021

Current Research in Pharmacology and Drug Discovery

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“…Dietary VitD (VitD2 or VitD3) is absorbed primarily via mixed micelles (21,22), although there is some indication that phospholipid vesicles may also be involved in this process. There are also reports of the involvement of active VitD metabolites in matrix vesicles involved in bone calcification (23). These biochemical factors make the study of VitD in phospholipid membranes relevant to several clinically significant questions.…”

Section: Introductionmentioning

confidence: 99%

Effect of cholecalciferol on unsaturated model membranes

Devarajan

Kim

Isakovic

et al. 2021

Chemistry and Physics of Lipids

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“…To explore the alternative source for islet β cells, we characterized adult peripheral blood insulin-producing cells (PB-IPC) from adult peripheral blood by virtue of their ability to attach to the hydrophobic plastic surface [ 30 ], which is a similar approach for an isolation of CB-SC [ 25 , 26 , 27 , 28 , 29 ]. PB-IPC displayed characteristics of islet β-cell progenitors including the expression of β cell-specific insulin gene-associated transcription factors and prohormone convertases, production of insulin, the ability to reduce hyperglycemia and the ability to migrate into pancreatic islets after transplantation into the streptozotocin (STZ)-induced diabetic mice [ 31 ]. In our recent study, PB-IPC have been treated with platelet-derived mitochondria to test the potential of improving islet β-cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

Generation of Multipotent Stem Cells from Adult Human Peripheral Blood Following the Treatment with Platelet-Derived Mitochondria

Song

et al. 2020

Cells

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Autologous stem cells are highly preferred for cellular therapy to treat human diseases. Mitochondria are organelles normally located in cytoplasm. Our recent studies demonstrated the differentiation of adult peripheral blood-derived insulin-producing cells (designated PB-IPC) into hematopoietic-like cells after the treatment with platelet-derived mitochondria. To further explore the molecular mechanism and their therapeutic potentials, through confocal and electron microscopy, we found that mitochondria enter cells and directly penetrate the nucleus of PB-IPC after the treatment with platelet-derived mitochondria, where they can produce profound epigenetic changes as demonstrated by RNA-seq and PCR array. Ex vivo functional studies established that mitochondrion-induced PB-IPC (miPB-IPC) can give rise to retinal pigment epithelium (RPE) cells and neuronal cells in the presence of different inducers. Further colony analysis highlighted the multipotent capability of the differentiation of PB-IPC into three-germ layer-derived cells. Therefore, these data indicate a novel function of mitochondria in cellular reprogramming, leading to the generation of autologous multipotent stem cells for clinical applications.

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Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation

Cited by 12 publications

References 49 publications

Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes

Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes

Effect of cholecalciferol on unsaturated model membranes

Generation of Multipotent Stem Cells from Adult Human Peripheral Blood Following the Treatment with Platelet-Derived Mitochondria

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