Insulin-like growth factor-I stimulates cell proliferation in the outer layer of Hertwig?s epithelial root sheath and elongation of the tooth root in mouse molars in vitro

Abstract

To elucidate the mechanism of root formation in tooth development, we examined the role of insulin-like growth factor I (IGF-I) on early root formation in mandibular first molar teeth from 5-day-old mice. Immunohistochemistry revealed the specific localization of the IGF-I receptor in Hertwig's epithelial root sheath (HERS) in the tooth root. The effect of IGF-I on root development, especially on HERS, was subsequently examined in vitro. The control culture showed normal development of HERS and the periodontium, resembling that in vivo. However, the presence of 100 ng/ml IGF-I resulted in elongation of HERS and increased cell proliferation in its outer layer. These effects were negated by the addition of antibodies specific for IGF-I. Thus, we propose that IGF-I is involved in early root formation by regulating the mitotic activity in the outer layer of HERS.

Cellular and molecular mechanisms of tooth root development

“…In addition to the signaling molecules mentioned above, studies have shown that IGF1 and HGF may also be involved in regulating root formation (Fujiwara et al, 2005;Sakuraba et al, 2012), although their precise function in regulating epithelial or mesenchymal cells is yet to be elucidated. Nonetheless, taking all of these studies together, we are beginning to understand the complex signaling network that regulates epithelial-mesenchymal interactions during root formation (summarized in Fig.…”

Cessation of Fgf10 signaling, resulting in a defective dental epithelial stem cell compartment, leads to the transition from crown to root formation

“…To label the mutant incisors growing under the kidney capsules, 1 mg/100 g (body weight) BrdU (Sigma-Aldrich, St Louis, MO, USA) was injected into the abdominal cavity of recipient mice (those transplanted with the mutant incisor germs), which were sacrificed 2 hours later, at which point the incisor immunostaining was carried out. In vitro cultures for observing root development of mouse molars were performed as previously described (Fujiwara et al, 2005). Explants from PN d3 and d5 mice were incubated for 1 day and then washed with Hanks' balanced salt solution in the presence of BrdU (0.5 mg/ml for 3 hours), embedded in paraffin, and serially sectioned into 5 m sections.…”

Retraction

“…Studies performed from the benchtop to the clinic have provided exciting possibilities for BMP-2 and IGF-1 to stimulate periodontal tissue repair (Vainio, et al, 1993;Yamaguchi, 1995;King and Hughes, 2001;Xu, et al, 2003;Fujiwara, et al, 2005;Ripamonti, et al, 2005;Popowics, et al, 2005;Soares, et al, 2005;Kaigler, et al, 2006).…”

“…During the past twenty years, many investigators have demonstrated the anabolic effects of locally application of many growth factors (GFs) on the promotion of periodontal attachment structures, namely alveolar bone, periodontal ligament (PDL) and tooth root cementum (Giannobile, 1996;King and Hughes, 2001;King and Cochran, 2002;Zhao, et al, 2002;Fujiwara, et al, 2005;Kaigler, et al, 2006). The mechanisms of GFs that control and enhance periodontal regeneration capacity are poorly understood; however, some studies have shown that the association of different GFs would enhance their activity in a synergistic manner compared to the activity of a single GF (Lynch, et al, 1991a(Lynch, et al, , 1991bShih, et al, 1996;Howell, et al, 1997;Zaman, et al, 1999;Ripamonti, et al, 2001;Puleo, 2004a, 2004b).…”