Leon E R, Iwasaki K, Komaki M, Kojima T, Ishikawa I
Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
J Periodontal Res. 2007 Dec;42(6):527-35. doi: 10.1111/j.1600-0765.2007.00977.x.
Human periodontal ligament cells are considered to be a key cell type in the regeneration of periodontal tissues because of their unique localization and stem cell-like properties. Interleukin-11 is a multifunctional cytokine known to participate actively in bone metabolism. The purpose of this study was to examine the effect of interleukin-11 on the osteoblastic differentiation of periodontal ligament cells.
Cultured periodontal ligament cells were stimulated with interleukin-11 and/or ascorbic acid, with or without inhibitors for type 1 collagen, janus kinase/signal transducers and activator of transcription, and mitogen-activated protein kinase (MAPK). Osteoblastic differentiation was investigated by examining the alkaline phosphatase activity and gene expression of Runx2, osteocalcin and bone sialoprotein using reverse transcription-polymerase chain reaction. Type 1 collagen and tissue inhibitor of metalloproteinase-1 production were measured using enzyme-linked immunosorbent assays.
Interleukin-11 enhanced alkaline phosphatase activity and Runx2, osteocalcin and bone sialoprotein gene expression in the presence of ascorbic acid. Interleukin-11 induced type 1 collagen and tissue inhibitor of metalloproteinase-1 production in periodontal ligament cells. Type 1 collagen inhibitor completely inhibited the alkaline phosphatase activity enhanced by interleukin-11 and ascorbic acid. Furthermore, janus kinase/signal transducers and activator of transcription and MAPK signaling inhibitors reduced interleukin-11/ascorbic acid-induced alkaline phosphatase activity in periodontal ligament cells.
Interleukin-11/ascorbic acid induced the osteoblastic differentiation of periodontal ligament cells through type 1 collagen production and janus kinase/signal transducers and activator of transcription, and MAPK signaling pathways were involved in this process. These findings suggest that interleukin-11 may function as an osteopromotive cytokine, stimulating the osteoblastic differentiation of periodontal ligament cells mainly through the synthesis of type 1 collagen and possibly by the induction of tissue inhibitor of metalloproteinase-1.
人牙周膜细胞因其独特的定位和干细胞样特性,被认为是牙周组织再生中的关键细胞类型。白细胞介素-11是一种已知积极参与骨代谢的多功能细胞因子。本研究的目的是检测白细胞介素-11对牙周膜细胞成骨分化的影响。
用白细胞介素-11和/或抗坏血酸刺激培养的牙周膜细胞,同时使用或不使用1型胶原、Janus激酶/信号转导子和转录激活子以及丝裂原活化蛋白激酶(MAPK)的抑制剂。通过逆转录-聚合酶链反应检测碱性磷酸酶活性以及Runx2、骨钙素和骨涎蛋白的基因表达,以研究成骨分化情况。使用酶联免疫吸附测定法测量1型胶原和金属蛋白酶组织抑制剂-1的产生量。
在存在抗坏血酸的情况下,白细胞介素-11增强了碱性磷酸酶活性以及Runx2、骨钙素和骨涎蛋白的基因表达。白细胞介素-11诱导牙周膜细胞产生1型胶原和金属蛋白酶组织抑制剂-1。1型胶原抑制剂完全抑制了白细胞介素-11和抗坏血酸增强的碱性磷酸酶活性。此外,Janus激酶/信号转导子和转录激活子以及MAPK信号抑制剂降低了白细胞介素-11/抗坏血酸诱导的牙周膜细胞碱性磷酸酶活性。
白细胞介素-11/抗坏血酸通过1型胶原的产生诱导牙周膜细胞的成骨分化,Janus激酶/信号转导子和转录激活子以及MAPK信号通路参与了这一过程。这些发现表明白细胞介素-11可能作为一种促骨细胞因子发挥作用,主要通过1型胶原的合成并可能通过诱导金属蛋白酶组织抑制剂-1来刺激牙周膜细胞的成骨分化。