Transcriptional regulation of bone sialoprotein gene expression by Osx

Yang, Ying; Huang, Yehong; Zhang, Li; Zhang, Chi

doi:10.1016/j.bbrc.2016.05.164

Cited by 17 publications

(16 citation statements)

References 23 publications

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“…Basal and stimulated ALP activity was respectively 47.20 ± 10.68 and 69.91 ± 12.72 UI/mg protein (p < 0.001), and BGP values were 8.43 ± 0.98 and 27.63 ± 2.99 ng/mg protein (p < 0.001). To investigate the role of BET on osteoblast differentiation, hOBs were cultured with 10 mM BET for 1, 3, 6 and 24 h. We firstly investigated BET action on crucial osteoblastic transcription factors: RUNX2 and OSX [15–19]. The real time PCR analysis showed that RUNX2 and OSX mRNAs expression was significantly increased after 1 h (p < 0.05; p < 0.001) and 3 h (p < 0.001; p < 0.001; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1a). Because the expression of many osteogenic proteins, including OPN and BSP, is directly controlled by RUNX2-OSX axis [18, 19], we determined BSP and OPN expression levels: BSP and OPN mRNA expressions increased significantly after 3 h of BET treatment (p < 0.001) and the increase of OPN mRNA lasted until 6 h (p < 0.01 Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…Since BET up regulates RUNX2 and OSX gene expression and promotes the synthesis of specific non collagenous bone proteins, like BSP and OPN, it is likely that this nutrient is involved in triggering major events in osteogenesis and bone remodeling, potentially restoring the negatively affected balance of bone remodeling during aging. RUNX2 and OSX are indeed key transcription factors of osteoblastic differentiation which activate the downstream processes of osteoblast maturation [15–19]; they also interact and coordinately regulate the expression of bone-specific genes [45]. Moreover, BSP and OPN are two non-collagenous proteins which serve as a matrix-associated signals presenting overlapping and multifunctional activities in bone with effects on bone formation, mineralization and remodeling [44].…”

Section: Discussionmentioning

confidence: 99%

“…In bone, ERKs promote the proliferation and differentiation of osteoblasts [43, 48], and mediates the response of bone to a variety of stimuli, including hormone/growth factor stimulation [49, 50], extracellular matrix–integrin binding [51] and mechanical loading [52]. In particular, ERK phosphorylates RUNX2, thus enhancing RUNX2 dependent gene expression [15–19, 46, 47, 53]. …”

Section: Discussionmentioning

confidence: 99%

“…RUNX2 is the main transcription factors inducing the osteogenic process [16] by activating other important osteoblast-specific transcription factors, like osterix (OSX) [17, 18]. During the differentiation of pre-osteoblasts into mature osteoblasts, RUNX2-OSX axis regulates the expression of bone marker proteins, including type I collagen, bone sialoprotein (BSP) and osteopontin (OPN) [15, 16, 19]. The effects of RUNX2 in bone development is positively regulated by ERKs cascade.…”

Section: Introductionmentioning

confidence: 99%

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Betaine promotes cell differentiation of human osteoblasts in primary culture

Villa¹,

Senesi

Montesano

et al. 2017

J Transl Med

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BackgroundBetaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation.MethodsThe effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery. Cells were treated with 10 mM BET at 5, 15, 60 min and 3, 6 and 24 h. The possible effects of BET on hObs differentiation were evaluated by real time PCR, western blot and immunofluorescence analysis. Calcium imaging was used to monitor intracellular calcium changes.ResultsReal time PCR results showed that BET stimulated significantly the expression of RUNX2, osterix, bone sialoprotein and osteopontin. Western blot and immunofluorescence confirmed BET stimulation of osteopontin protein synthesis. BET stimulated ERK signaling, key pathway involved in osteoblastogenesis and calcium signaling. BET induced a rise of intracellular calcium by means of the calcium ions influx from the extracellular milieu through the L-type calcium channels and CaMKII signaling activation. A significant rise in IGF-I mRNA at 3 and 6 h and a significant increase of IGF-I protein at 6 and 24 h after BET stimulus was detected. Furthermore, BET was able to increase significantly both SOD2 gene expression and protein content.ConclusionsOur study showed that three signaling pathways, i.e. cytosolic calcium influx, ERK activation and IGF-I production, are enhanced by BET in human osteoblasts. These pathways could have synergistic effects on osteogenic gene expression and protein synthesis, thus potentially leading to enhanced bone formation. Taken together, these results suggest that BET could be a promising nutraceutical therapeutic agent in the strategy to counteract the concomitant and interacting impact of sarcopenia and osteoporosis, i.e. the major determinants of senile frailty and related mortality.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Betaine promotes cell differentiation of human osteoblasts in primary culture

Villa¹,

Senesi

Montesano

et al. 2017

J Transl Med

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Cyclin‐dependent kinase 8/19 inhibition suppresses osteoclastogenesis by downregulating RANK and promotes osteoblast mineralization and cancellous bone healing

Amirhosseini

Bernhardsson

Lång

et al. 2019

Journal Cellular Physiology

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Cyclin‐dependent kinase 8 (CDK8) is a mediator complex‐associated transcriptional regulator that acts depending on context and cell type. While primarily under investigation as potential cancer therapeutics, some inhibitors of CDK8—and its paralog CDK19—have been reported to affect the osteoblast lineage and bone formation. This study investigated the effects of two selective CDK8/19 inhibitors on osteoclastogenesis and osteoblasts in vitro, and further evaluated how local treatment with a CDK8/19 inhibitor affects cancellous bone healing in rats. CDK8/19 inhibitors did not alter the proliferation of neither mouse bone marrow–derived macrophages (BMMs) nor primary mouse osteoblasts. Receptor activator of nuclear factor κΒ (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis from mouse BMMs was suppressed markedly by inhibition of CDK8/19, concomitant with reduced tartrate‐resistant acid phosphatase (TRAP) activity and C‐terminal telopeptide of type I collagen levels. This was accompanied by downregulation of PU.1, RANK, NF‐κB, nuclear factor of activated T‐cells 1 (NFATc1), dendritic cell‐specific transmembrane protein (DC‐STAMP), TRAP, and cathepsin K in RANKL‐stimulated BMMs. Downregulating RANK and its downstream signaling in osteoclast precursors enforce CDK8/19 inhibitors as anticatabolic agents to impede excessive osteoclastogenesis. In mouse primary osteoblasts, CDK8/19 inhibition did not affect differentiation but enhanced osteoblast mineralization by promoting alkaline phosphatase activity and downregulating osteopontin, a negative regulator of mineralization. In rat tibiae, a CDK8/19 inhibitor administered locally promoted cancellous bone regeneration. Our data indicate that inhibitors of CDK8/19 have the potential to develop into therapeutics to restrict osteolysis and enhance bone regeneration.

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