title: Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human osteoblast-like cells (Saos-2).
abstract: A lower bone mass accompanied by a higher bone fragility with increased risk of fracture are observed in individuals with type 1 diabetes mellitus. Low C-peptide levels are associated with low lumbar mineral density in postmenopausal woman. In this work, we investigated the role of C-peptide on the osteoblast cell biology in vitro. We examined intracellular pathways and we found that C peptide activates ERK1/2 in human osteoblast-like cells (Saos-2). We also observed that proinsulin C-peptide prevents a reduction of type I collagen expression and decreases, in combination with insulin, receptor activator of nuclear factor-κB (RANKL) levels. In this work we show for the first time that Cpeptide activates a specific intracellular pathway in osteoblasts and it modulates the expression of protein involved in bone remodeling. Our results suggest that both C-peptide may have a role in bone metabolism. Further studies are needing to fully clarify its role.
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Russo
authors.affiliation: Department of Health Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Lazzaro
authors.affiliation: Internal and Emergency Medicine, and Ce.R.C.A. Clinical Institute "Beato Matteo", Vigevano, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Gazzaruso
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Maurotti
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Yvelise
authors.initials: Y
authors.lastname: Ferro
authors.affiliation: Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
authors.forename: Piero
authors.initials: P
authors.lastname: Pingitore
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fumo
authors.affiliation: Internal and Emergency Medicine, and Ce.R.C.A. Clinical Institute "Beato Matteo", Vigevano, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Internal and Emergency Medicine, and Ce.R.C.A. Clinical Institute "Beato Matteo", Vigevano, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Gallotti
authors.affiliation: Internal and Emergency Medicine, and Ce.R.C.A. Clinical Institute "Beato Matteo", Vigevano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Zambianchi
authors.affiliation: Internal and Emergency Medicine, and Ce.R.C.A. Clinical Institute "Beato Matteo", Vigevano, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Fodaro
authors.affiliation: Department of Biomedical, Surgical and Dental Science, University of Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Galliera
authors.affiliation: Department of Health Biomedical Science, University of Milan, Italy.
authors.forename: Monica Gioia
authors.initials: MG
authors.lastname: Marazzi
authors.affiliation: Department of Health Biomedical Science, University of Milan, Italy.
authors.forename: Massimiliano Marco
authors.initials: MM
authors.lastname: Corsi Romanelli
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Giannini
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy; Department of Molecular and Clinical Medicine, University of Gothenburg, Sweden.
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.affiliation: Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Pujia
authors.affiliation: Department of Clinical and Experimental Medicine, University "Magna Graecia" of Catanzaro, Italy. Electronic address: tmontalcini@unicz.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montalcini
mesh_terms: D016723:Bone Remodeling / Q000502:physiology; D002096:C-Peptide / Q000378:metabolism*; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D002096:C-Peptide; D024042:Collagen Type I; D007328:Insulin; D016328:NF-kappa B; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: Insulin; Osteoporosis; Proinsulin C-peptide; RANKL; Type I collagen