Identification of IGF-I in the Calvarial Suture of Young Rats: Histochemical Analysis of the Cranial Sagittal Sutures in a Hyperthyroid Rat Model

Abstract

Premature closure of cranial sutures has been known as one of the complications of juvenile or congenital hyperthyroidism. Thyroid hormone is an anabolic agent for bone formation in the early stages of childhood development. In children, excess thyroid hormone acts as an acceleration factor for the skeletal bone, whereas in adult hyperthyroidism, it causes bone mineral loss due to the high turnover rate of bone formation and consequently bone resorption. In addition, there are numerous literature descriptions concerning the interactions among bone metabolism, hormones, and growth factors, among which insulin-like growth factor I (IGF-I) is the most abundantly found growth factor in osteoblasts and in bone models in vivo. We therefore investigated whether or not the cranial sutures show accelerated closure and how the local growth factors or cytokines participate and function in local bone metabolism after administration of exogenous excess thyroid hormone in a rat model. A total of 60 female Wistar rats, aged 10 days, were divided into two groups, the triiodothyronine (T3)-treated group (n = 30, T3 0.1 microgram/gm of body weight per day) and the control group (n = 30, saline vehicle only), and were maintained and subsequently sacrificed at 15, 30, and 60 days. The parameters of cranial width derived from the morphologic measurements of the skull indicated that the lambda-asterion distance at 30 days and the pterion-bregma distance at 60 days in the T3-treated group were significantly decreased compared with those of the control group. Furthermore, the fluorescent histologic findings showed fluorescent labeling with no interruption along the suture edges, suggesting continuous bone formation, and displayed narrowing of the suture gap of the sagittal suture in the T3-treated group. Tartrate resistant acid phosphatase staining showed very little osteoclastic activity in the sagittal suture, especially in the T3-treated group. The intensity of immunohistochemical staining of IGF-I was markedly increased in the suture margins of the T3-treated group. There were no significant differences observed either in the skull base measurements or in the histologic and histochemical findings of the skull base or the coronal suture between the groups. More significantly, excess administration of thyroid hormone enhanced the cranial sagittal suture closure; therefore, it was proposed that local IGF-I plays an important role in sagittal sutural bone formation.