IntroductionLeptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa.MethodsImmunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively.ResultsOb-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin.ConclusionTopically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.

No abstract

Postmenopausal osteoporosis is a high turnover type of osteoporosis induced by estrogen deficiency following menopause. In this type of osteoporosis, the osteoblastic activity is known to be elevated even though bone resorption by osteoclasts eventually exceeds bone formation by osteoblasts, resulting in the deterioration of the bone structure. Although the mechanisms underlying the progression of bone resorption in this disease are relatively well understood, the mechanisms underlying the elevated osteoblastic activity are yet to be elucidated. The purpose of this study is to investigate the possibility that leptin, a 16 kDa circulating hormone secreted mainly by white adipose tissue, is involved in the development and/or progression of the high turnover type of osteoporosis. Immunohistochemical analysis and ELISA were used to examine the expression of leptin in bones of ovariectomized mice. To investigate the effect of leptin on proliferation and osteoblastic differentiation of bone marrow stromal cells, cell proliferation assay and real-time RT-PCR analysis were performed using a mouse bone marrow stromal cell line, MMSC3. Immunohistochemistry and ELISA revealed enhanced expression of leptin in bone marrows of ovariectomized mice. A cell proliferation assay detected no significant effect of leptin on the proliferation of MMSC3 cells. In contrast, real-time RT-PCR revealed that leptin promoted the osteoblastic differentiation of this cell line. Estrogen depletion caused by ovariectomy induces the upregulation of leptin expression in the bone marrow cavity, which leads to the elevated osteoblastic activity observed in the early phase of high turnover type osteoporosis of ovariectomized mice.