IGFs, IGFBPs, IGF-Binding Sites and Biochemical Markers of Bone Metabolism during Differentiation in Human Pulp Fibroblasts

Abstract

Objective: To investigate the role of the insulin-like growth factors (IGF) system during the differentiation of human pulp-derived fibroblasts (HPF). Methods: Primary HPF were cultured for 24 days in DMEM medium with IGF-I or IGF-II (50 ng/ml each). Cell growth and morphology, alkaline phosphatase (ALP) activity, the concentration of free deoxypyridinoline (DPD), IGF-I, -II, IGFBP-2 and -3 were studied. The number of ¹²⁵I-IGF-I binding sites was estimated by Scatchard analysis. Results: Light-microscopically visible nodules emerged during differentiation. Simultaneously, the ALP activity increased steadily between days 8 and 24, while the DPD concentration decreased by about 50%. The HPF produced high concentrations of IGF-II (2.00–1.30 µg/10⁶ cells) but low IGF-I, IGFBP-2. IGFBP-2 was not changed, IGFBP-3 increased by 65% during differentiation. The number of IGF binding sites increased from 8,500 ± 55 per cell (day 8) up to 22,000 ± 570 (day 24). Conclusion: The increasing number of IGF-binding sites accompanied by alterations in the biochemical bone markers during the differentiation of HPF suggests an autocrine/paracrine role for the IGFs in the formation of dentinal hard tissue.

Insulin-Like Growth Factor Axis Expression in Dental Pulp Cells Derived From Carious Teeth

“…We have recently confirmed that IGF2 peptide is present at 10-fold higher concentrations in differentiated DPCs compared to cells grown under basal conditions (Al-Khafaji et al submitted for publication). We believe our data represent the first demonstration of increased IGF2 expression under mineralization conditions in DPCs and confirm previous findings that IGF2 is the main IGF species expressed in dental pulp (Reichenmiller et al, 2004 ). IGF2 may be sequestered in the matrix during dentin formation and released during demineralization of dentin.…”

IGFBP-2 and -3 co-ordinately regulate IGF1 induced matrix mineralisation of differentiating human dental pulp cells

“…Conversley IGF-2 and IGF-1R were expressed at moderate to high levels in our experiments confirming previous reports (Caviedes-Bucheli et al, 2004, Shi et al, 2001). Both IGF-1 and IGF-2 (acting via the IGF-1R) can induce ALP activity in canine dental pulp cells (Onishi et al, 1999) and IGF-2 secretion was reported during matrix mineralisation of human dental pulp derived fibroblasts (Reichenmiller et al, 2004). IGF axis components are present in other dental structures with IGF-1 and -2 along with all six IGFBPs present in the ECM of the periodontal ligament and IGF-1R present on the surface of periodontal ligament derived fibroblasts (Gotz et al, 2006).…”

Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction

“…However, DPSC show higher self‐renewal ability, immunomodulatory capacity, and proliferation in vitro than BM‐MSC, and they differentiate preferentially to osteoblasts rather than to adipocytes [6, 15]. These cells, like BM‐MSC, are able to secrete vascular endothelial growth factor (VEGF) [16, –18], insulin‐like growth factor‐1 (IGF‐1) and ‐2 (IGF‐2) [13, 19, 20], stem cell factor (SCF), and granulocyte‐colony stimulation factor [21, 22], all of which can exert proangiogenic, antiapoptotic, and cardioprotective actions [3, 23, 24]. Thus, the aim of this study was to determine whether DPSC could be useful for cardiac repair, in a rat model of MI.…”