Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human osteoblast-like cells (Saos-2)

Russo, Cristina; Lazzaro, Veronica; Gazzaruso, Carmine; Maurotti, Samantha; Ferro, Yvelise; Pingitore, Piero; Fumo, Francesca; Coppola, Adriana; Gallotti, Pietro; Zambianchi, V.; Fodaro, Mariangela; Galliera, Emanuela; Marazzi, Monica Gioia; Romanelli, Massimiliano Marco Corsi; Giannini, Sandro; Romeo, Stefano; Pujia, Arturo; Montalcini, Tiziana

doi:10.1016/j.mce.2016.12.012

Cited by 12 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The value recorded at day 14 is significantly higher for cells which were cultured in differentiation media D2, meaning that the differentiation process was enhanced by the presence of AA, β‐GP and dexamethasone (P<0.01). This is probably due to the presence of dexamethasone, which has been reported to increase the ALP activity and produce a more differentiated phenotype .…”

Section: Resultsmentioning

confidence: 97%

Electrochemical Monitoring of Saos‐2 Cell Differentiation on Pyrolytic Carbon Electrodes

et al. 2018

View full text Add to dashboard Cite

In this study we establish an electrochemical platform based on two dimensional (2D) pyrolytic carbon electrodes for in vitro analysis of osteoblast differentiation. Electrochemical impedance spectroscopy (EIS) was used to monitor cell adhesion and proliferation, while an electrochemical assay based on square wave voltammetry (SWV) was applied to measure the activity of the differentiation marker alkaline phosphatase (ALP). 2D pyrolytic carbon electrodes were fabricated and used to monitor Saos‐2 cell differentiation for a period of up to 21 days. With this method it was possible to detect a faster increase of ALP activity for cells cultured in medium supplemented with differentiation factors compared to cells cultured in growth medium. This was confirmed by the results obtained with Alizarin Red staining, showing that cells subjected to osteogenic medium went through the entire differentiation process, from proliferation to mineralization. Finally, for the first time, real‐time monitoring of ALP activity combined with continuous EIS monitoring of the same cell culture was achieved using the pyrolytic carbon electrodes.

show abstract

Section: Resultsmentioning

confidence: 97%

Electrochemical Monitoring of Saos‐2 Cell Differentiation on Pyrolytic Carbon Electrodes

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Effective treatments may increase the trabecular bone by thickening the trabeculae. By its action on the osteoblasts [25], we hypothesise that C-peptide therapy led to the deposition of the new bone matrix in layers around the trabeculae, which thus became thick at the expense of the spaces between them. It is possible that the effects of C-peptide may also be exerted via blood glucose control.…”

Section: Discussionmentioning

confidence: 99%

“…Through its effects on osteoblasts [25], we hypothesise that C-peptide, could, in turn, stimulate bone marrow-derived cells differentiation. Of course, we cannot confirm that this effect improves the trabecular bone.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of C-peptide replacement therapy on bone microarchitecture parameters in streptozotocin-diabetic rats

Maurotti

Russo

Musolino

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Pathological pathways involved in the development of diabetic complications are still unclear.Several studies suggested a pathogenic role of C-peptide deficiency in vascular and neuropathic complications. However, to date, the role of C-peptide on diabetes-related bone loss has not been investigated. The objective of this study was to test the effects of a 6-week regimen of rat C-peptide infusion on bone by combining micro-CT imaging with histological testing.Twenty-three, four-month-old male Wistar rats were randomly divided into three groups: Normal control group; Sham diabetic control group; Diabetic plus C-peptide group. Diabetes was induced by injection of streptozotocin. Rat C-peptide was delivered via subcutaneously osmopumps. We assessed several trabecular microarchitectural parameters and cellular and matrix proteins in bone tissue sections.At the end of the study, both the normal control and diabetic plus C-peptide groups had a higher tibia weight than the diabetic control group (p = 0.05 and p = 0.02, respectively). C-peptide levels significantly and positively correlated with the trabecular thickness (r= 0.45, p=0.08) and negatively with structure model index (r= -0.40, p=0.09). Furthermore, it positively correlated with one of the histological assessments (i.e. PLIN1 score; p=0.02). Micro-CT evaluation showed significant intergroup differences in trabecular thickness (p=0.02), trabecular space (p = 0.05) and cross-sectional thickness (p=0.05). Diabetic plus C-peptide group showed a higher trabecular thickness (p<0.001), cross-sectional thickness (p=0.03) and a lower trabecular space (p=0.05) than the normal control group. Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison to the diabetic control group (p = 0.045 and p = 0.034).For the first time we demonstrated that the diabetic rats receiving rat C-peptide had higher quality of trabecular bone, than diabetic rats not receiving it. C-peptide could have a role in the prevention of diabetes-related bone loss.

show abstract

“…Russo et al clarified how C-peptide can activate and proliferate the intracellular pathways of human osteoblast-like cells (Saos-2), providing additional information about the expression of the bone extracellular matrix proteins. These authors have shown, for the first time, that C-peptide activates a specific intracellular pathway in osteoblasts and also that, together with insulin, it can influence collagen biosynthesis and RANKL expression [108].…”

Section: Cell Signalling Pathways Of Human Proinsulin C-peptide In Vamentioning

confidence: 99%

Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection

Souto

Campos

Fangueiro

et al. 2020

IJMS

View full text Add to dashboard Cite

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal–regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.

show abstract

Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human osteoblast-like cells (Saos-2)

Cited by 12 publications

References 33 publications

Electrochemical Monitoring of Saos‐2 Cell Differentiation on Pyrolytic Carbon Electrodes

Electrochemical Monitoring of Saos‐2 Cell Differentiation on Pyrolytic Carbon Electrodes

Effects of C-peptide replacement therapy on bone microarchitecture parameters in streptozotocin-diabetic rats

Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection

Contact Info

Product

Resources

About