RESUMO
Transducing-like enhancer of split 3 (TLE3), one of the Groucho/TLE family members, targets Runx2 transcription and suppresses osteoblast differentiation in bone marrow stromal cells (BMSCs). Here, we identify Wnt responsive elements of the TLE3 promoter region through comparative genomic and functional analyses and show that expression of TLE3 is increased by Wnt signaling, which is important for osteoblast differentiation. We also demonstrated that TLE3 is able to suppress canonical Wnt signaling in BMSCs. Taken together, our data suggest that induction of TLE3 by Wnt signaling is part of a negative feedback loop active during osteoblast differentiation.
Assuntos
Proteínas Correpressoras/genética , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais , Proteínas Wnt/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Diferenciação Celular , Linhagem Celular , Sequência Conservada , Genômica , Humanos , Camundongos , Dados de Sequência Molecular , Osteoblastos/citologia , Elementos de Resposta/genética , beta Catenina/metabolismoRESUMO
Recent studies have indicated that acetylcholine (ACh) plays a vital role in various tissues, while the role of ACh in bone metabolism remains unclear. Here we demonstrated that ACh induced cell proliferation and reduced alkaline phosphatase (ALP) activity via nicotinic (nAChRs) and muscarinic acetylcholine receptors (mAChRs) in osteoblasts. We detected mRNA expression of several nAChRs and mAChRs. Furthermore, we showed that cholinergic components were up-regulated and subunits/subtypes of acetylcholine receptors altered during osteoblast differentiation. To our knowledge, this is the first report demonstrating that osteoblasts express specific acetylcholine receptors and cholinergic components and that ACh plays a possible role in regulating the proliferation and differentiation of osteoblasts.
Assuntos
Acetilcolina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Receptores Colinérgicos/genética , Células 3T3 , Acetilcolina/análogos & derivados , Acetilcolinesterase/genética , Fosfatase Alcalina/metabolismo , Animais , Western Blotting , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colina O-Acetiltransferase/genética , Colinérgicos/farmacologia , Ciclina D1/genética , Ciclina D1/metabolismo , Relação Dose-Resposta a Droga , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Receptores Colinérgicos/metabolismo , Receptores Muscarínicos/genética , Receptores Muscarínicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Simportadores/genética , Proteínas Vesiculares de Transporte de Acetilcolina/genéticaRESUMO
A new concept of IgG4-related disease characterized by a high serum IgG4 level and tissue infiltration of IgG4-positive plasmacytes that can involve salivary glands has been proposed. In this article, 2 patients with IgG4-related sclerosing sialadenitis involving the submandibular glands are reported. One patient presented with bilateral and painless swelling of the submandibular glands. He had already been treated with systemic prednisolone owing to the occurrence of retrobulbar neuritis. Laboratory examinations showed high serum IgG4 concentrations, and a biopsy of the submandibular gland revealed the infiltration of IgG4-positive plasmacytes. Abdominal computerized tomography demonstrated tumefaction in the tail of the pancreas, thus suggesting localized autoimmune pancreatitis. The other patient also showed bilateral and painless swelling of the submandibular glands, but there was no involvement of any other organs. These patients were effectively treated with corticosteroids, which resulted in a reduction of the swelling of the submandibular gland and increased saliva. When a patient is suspected of having sclerosing sialadenitis, it is important to consider that the patient may have a systemic IgG4-related plasmacytic disease.
Assuntos
Imunoglobulina G/sangue , Sialadenite/sangue , Doenças da Glândula Submandibular/sangue , Idoso , Anti-Inflamatórios/uso terapêutico , Doenças Autoimunes/diagnóstico por imagem , Biópsia , Doença Crônica , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Mikulicz/diagnóstico , Pancreatite/diagnóstico por imagem , Pancreatite/imunologia , Paraproteinemias/diagnóstico , Plasmócitos/patologia , Prednisolona/uso terapêutico , Radiografia Abdominal , Esclerose , Sialadenite/patologia , Doenças da Glândula Submandibular/patologia , Tomografia Computadorizada por Raios XRESUMO
Recent studies have suggested that nicotine critically affects bone metabolism. Many studies have examined the effects of nicotine on proliferation and differentiation, but the underlying molecular mechanisms remain unclear. We examined cell cycle regulators involved in the proliferation and differentiation of MC3T3-E1 cells. Nicotine induced cell proliferation in association with p53 down-regulation and cyclin D1 up-regulation. In differentiated cells, nicotine reduced alkaline phosphatase activity and mineralized nodule formation in dose-dependent manners. Furthermore, p53 expression was sustained in nicotine-treated cells during differentiation. These findings indicate that nicotine promotes the cell cycle and inhibits differentiation in association with p53 regulation in pre-osteoblastic cells.
