Effects of recombinant human parathyroid hormone (1-34)on cell proliferation, chemokine expression and the Hedgehog pathway in keratinocytes

Abstract

Psoriasis is an autoimmune disease involving the excessive proliferation of keratinocytes mediated by T-cells. Parathyroid hormone (PTH) has been identified as an essential factor in the treatment of psoriasis. In the present study, the mechanism underlying the effect of recombinant human parathyroid hormone (rhPTH) (1-34) in keratinocytes was investigated. The effects of rhPTH (1-34) on cell proliferation, cell cycle, and the secretion and expression of C-X-C motif chemokine 11 (CXCL11) and components of the Hedgehog signaling pathway were examined in HaCaT cells by MTT assay, flow cytometric analysis, ELISA and gene chip analysis. The data showed that rhPTH (1-34) significantly inhibited keratinocyte proliferation at concentrations >8×10−7 mol/l. rhPTH (1-34) induced G1 phase arrest of the cell cycle in the keratinocytes. The secretion of CXCL11 in tumor necrosis factor (TNF)-α-induced keratinocytes was downregulated by rhPTH (1-34) in a dose-dependent manner, compared with that in keratinocytes treated with TNF-α alone. It was also found that rhPTH (1-34) inhibited the expression of CXCL11 in the HaCaT cells. rhPTH (1-34) also affected the Hedgehog signaling pathway specifically by regulating the expression of associated genes. In conclusion, these data suggested that rhPTH (1-34) inhibited cell proliferation, and the secretion and expression of CXCL11 in HaCaTs. rhPTH (1-34) also altered the expression of associated genes in the Hedgehog pathway. Therefore, rhPTH (1-34) can be considered as a novel therapeutic agent for the treatment of psoriasis.

Intermittent parathyroid hormone enhances the healing of medication-related osteonecrosis of the jaw lesions in rice rats

“…In addition, the response of the oral epithelium to PTH was significantly less in the presence of ZOL than in the absence of ZOL. Contrasting findings have been reported in an in vitro study, in which treatment with PTH (1–34) inhibited the proliferation of keratinocytes in a dose-dependent manner ( 65 ). The differences in the proliferative capacity may be due to the mode in that PTH is administered, considering that continuous and intermittent administration of PTH has contrasting catabolic and anabolic effects on bone ( 101 – 103 ).…”

“…On the contrary, PTH and PTH-related peptides (PTHrp) reduce inflammation and promote wound healing in the femur, tibia and periodontium (58)(59)(60)(61). Furthermore, PTH and PTHrp affect the proliferation of epithelial and mesenchymal cells but with opposite effects depending on cell and tissue types (61)(62)(63)(64)(65)(66)(67)(68)(69). The effect of iPTH on the oral epithelium is undefined.…”

PTH Derivative promotes wound healing via synergistic multicellular stimulating and exosomal activities

“…In addition, there is evidence that PTH promotes fibrogenesis and collagen deposition [18,19]. PTH1R, a major receptor of PTH, has been found to be expressed in endothelial cells, fibroblasts and epithelial cells, which indicate the activating basis of application of PTH in skin tissue [20][21][22][23]. Therefore, we hypothesize that PTH might promote wound healing via multicellular stimulation and multilayer skin tissue repair.…”

PTH Derivative Promotes Wound Healing via Synergistic Multicellular Stimulating and Exosomal Activities

“…In addition, there is evidence that PTH promotes fibrogenesis and collagen deposition (18,19). PTH1R, a major receptor of PTH, has been found to be expressed in endothelial cells, fibroblasts and epithelial cells, which indicate the activating basis of application of PTH in skin tissue (20)(21)(22)(23). Therefore, we hypothesize that PTH might promote wound healing via multicellular stimulation and multilayer skin tissue repair.…”