Dimethyl sulfoxide as an inducer of differentiation in preosteoblast MC3T3‐E1 cells

Cheung, William M.W.; Ng, WS; Kung, Awc

doi:10.1016/j.febslet.2005.11.062

Cited by 41 publications

(31 citation statements)

References 30 publications

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“…It seems likely that DMSO-treated cells achieved a heightened state of differentiation reflected by an enhanced capacity to mineralize the surrounding extracellular matrix. Cheung et al (12) examined Runx2 and osterix induction by DMSO in normal ␣-MEM at 5 days only; Runx2 (1.89-fold) and osterix (1.39-fold) induction by DMSO was significant. In contrast, we examined the effect of DMSO on target gene expression using a number of target genes at numerous time points in OM; in particular, we observed strong induction of osterix by DMSO over the entire time period of mineralization, including days 3 and 5.…”

Section: Discussionmentioning

confidence: 99%

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Myocyte Enhancer Factor 2C, an Osteoblast Transcription Factor Identified by Dimethyl Sulfoxide (DMSO)-enhanced Mineralization

Stephens

Hobbs

et al. 2011

Journal of Biological Chemistry

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Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem cell-mediated therapies for fracture and other orthopedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of stimulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase activity and extracellular matrix mineralization. Furthermore, similar DMSOmediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1, we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among the numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblastlike cells in mouse mandible, cortical, and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased alkaline phosphatase activity, and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. A flow on knockdown of bone-specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c, suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts.Skeletal patterning and subsequent cellular differentiation during development is a complex process involving the activation and suppression of gene regulatory programs leading to bone formation (1). Once fully developed, bone remains a dynamic tissue by undergoing continual remodeling, which functions to repair microarchitectural defects and maintain skeletal integrity (2). Numerous cell types are involved in the formation and homeostasis of the skeleton. Among these are osteoblasts (bone-forming cells), which differentiate from committed mesenchymal osteoprogenitor cells (1). The differentiation of osteoblasts is a highly coordinated process involving a clearly defined temporal sequence of events characterized by the commitment, proliferation, and subsequent maturation of precursor cells into terminally differentiated osteoblasts (3, 4). During this process, early differentiating cells undergo proliferation and secrete a collagen type 1-rich extracellular matrix. In the next phase, cellular proliferation decreases, and the cells express factors involved in matrix maturation such as alkaline phosphatase. In the final stage, osteoblasts initiate matrix mineralization and express factors such as integrin-binding sialoprotein and osteocalcin (3-5).Osteoblast differentiation is tightly coordinated by the activit...

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Section: Discussionmentioning

confidence: 99%

“…Currently, DMSO is used as a cryo-preserving agent in cell banking (11) commonly at 10% concentrations that are then injected directly into the patient. Notably, DMSO is reported to stimulate osteoblast differentiation in MC3T3-E1, a mouse pre-osteoblast cell line, through ERK activation of transcription factors Runx2 and osterix (12).…”

mentioning

confidence: 99%

Myocyte Enhancer Factor 2C, an Osteoblast Transcription Factor Identified by Dimethyl Sulfoxide (DMSO)-enhanced Mineralization

Stephens

Hobbs

et al. 2011

Journal of Biological Chemistry

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“…Protein kinase C (PKC) and/or PKD have been known to be associated with osteoblastic differentiation (18)(19)(20). To investigate whether PKC or PKD mediate the Rh2(S)-induced differentiation and mineralization of osteoblastic MC3T3-E1 cells, two different staurosporine-derived inhibitors were utilized: Go6983 for PKCα, βI, βII, δ and γ and Go6976 for PKCα, βI and PKCµ/PKD.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rh2(S) induces differentiation and mineralization of MC3T3-E1 cells through activation of the PKD/AMPK signaling pathways

Kim

Park²,

Jung³

et al. 2011

Int J Mol Med

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Abstract. As part of our search for biologically active anti-osteoporotic agents that enhance differentiation and mineralization of osteoblastic MC3T3-E1 cells, we identified the ginsenoside Rh2(S). Mostly known to exhibit beneficial effects in cancer prevention and metabolic diseases, Rh2(S) is one of the most active ginsenosides. Here, we show that Rh2(S) stimulates osteoblastic differentiation and mineralization, manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and von Kossa/Alizarin Red staining, respectively. Rh2(S) also activated protein kinase D (PKD) and AMP-activated protein kinase (AMPK) in a timeand concentration-dependent manner, and Rh2(S)-induced differentiation and mineralization of osteoblastic cells were significantly abolished in the presence of specific inhibitors; Go6976 for PKD and Ara-A for AMPK. Furthermore, Go6976 suppressed Rh2(S)-mediated activation of AMPK, indicating that PKD may be an upstream signal for AMPK in Rh2(S)-induced differentiation and mineralization of MC3T3-E1 cells. Taken together, these results indicate that Rh2(S) induces the differentiation and mineralization of MC3T3-E1 cells through activation of PKD/AMPK signaling pathways. These findings provide a molecular basis for the osteogenic effect of Rh2(S).

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“…The proposed negative role of PKCμ in osteogenesis is in contrast to what has been reported previously, where PKCμ was shown to be involved in activating MC3T3 osteogenic differentiation [144,145]. Furthermore, Cecil and colleagues concluded that PKCμ is implicated in BMP-2 and IGF-I induced RUNX2 activity in hMSCs and mineralization using a 10µM dose of Gö6976 to demonstrate this [146].…”

Section: Discussionmentioning

confidence: 92%

“…Some reports show that certain PKC isozymes are involved in osteogenic differentiation or osteoblast proliferation. For instance, PKCδ and PKCμ, are known to be involved in osteogenic differentiation in murine cells and animal models and PKCα has been implicated in human osteoblasts proliferation [98,100,144]. We treated hMSCs with PKC activators and inhibitors to investigate cell proliferation and differentiation in vitro, and observed that different PKC subfamilies had opposite roles in ALP expression and mineralization.…”

Section: Improving Hmsc Osteogenic Differentiationmentioning

confidence: 99%

Bioluminescence imaging in bone tissue engineering

Li¹

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Dimethyl sulfoxide as an inducer of differentiation in preosteoblast MC3T3‐E1 cells

Cited by 41 publications

References 30 publications

Myocyte Enhancer Factor 2C, an Osteoblast Transcription Factor Identified by Dimethyl Sulfoxide (DMSO)-enhanced Mineralization

Myocyte Enhancer Factor 2C, an Osteoblast Transcription Factor Identified by Dimethyl Sulfoxide (DMSO)-enhanced Mineralization

Ginsenoside Rh2(S) induces differentiation and mineralization of MC3T3-E1 cells through activation of the PKD/AMPK signaling pathways

Bioluminescence imaging in bone tissue engineering

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