The putative role of insulin-like growth factor (IGF)-binding protein 5 independent of IGF in the maintenance of pulpal homeostasis in mice.

Although insulin-like growth factor binding protein 5 (IGFBP5) may play a crucial role in activating the functions of periodontal and bone marrow stem cells, the factors responsible for regulating the maintenance of dental pulp stem cells (DPSCs) remain to be clarified. This study aimed to elucidate the role of IGFBP5 in maintaining pulpal homeostasis during tooth development and pulpal healing after tooth injury in doxycycline-inducible TetOP-histone 2B (H2B)-green fluorescent protein (GFP) transgenic mice (GFP expression was induced at E14.5 or E15.5) by using TUNEL assay, RT-PCR, in situ hybridization for Igfbp5, and immunohistochemistry for IGFBP5, Nestin, and GFP. To observe the pulpal response to exogenous stimuli, the roots of the maxillary first molars were resected, and the coronal portion was autografted into the sublingual region. Intense IGFBP5/Igfbp5 expression was observed in cells from the center of the pulp tissue and the subodontoblastic layer in developing teeth during postnatal Week 4. Intense H2B-GFP-expressing label-retaining cells (LRCs) were localized in the subodontoblastic layer in addition to the center of the pulp tissue, suggesting that slowly dividing cell populations reside in these areas. During postoperative days 3-7, the LRCs were maintained in the dental pulp, showed an IGFBP5-positve reaction in their nuclei, and lacked a TUNEL-positive reaction. In situ hybridization and RT-PCR analyses confirmed the expression of Igfbp5 in the dental pulp. These findings suggest that IGFBP5 play a pivotal role in regulating the survival and apoptosis of DPSCs during both tooth development and pulpal healing following tooth injury.

Circulating miR-143-3p inhibition protects against insulin resistance in Metabolic Syndrome via targeting of the insulin-like growth factor 2 receptor.

Metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including obesity, dyslipidemia, hyperglycemia, and hypertension. Here, we report that 27 microRNAs were found to be expressed differently in serum and urine samples of MetS patients compared to control subjects on microarray analysis. Further qualitative real time- polymerase chain reaction analyses confirmed that circulating levels of miR-143-3p were significantly elevated in MetS patients compared with controls, both in serum and urine samples. After accounting for confounding factors, high levels of miR-143-3p remained an independent risk factor for insulin resistance. Inhibition of miR-143-3p expression in mice protected against development of obesity-associated insulin resistance. Furthermore, we demonstrated that insulin-like growth factor 2 receptor (IGF2R) was among the target genes of miR-143-3p by searching 3 widely used bioinformatics databases and preliminary validation. Our experiments suggest that knockdown of circulating miR-143-3p may protect against insulin resistance in the setting of MetS via targeting of IGF2R and activation of the insulin signaling pathway. Our results characterize the miR-143-3p-IGF2R pathway as a potential target for the treatment of obesity-associated insulin resistance.