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1.
Dev Dyn ; 250(4): 574-583, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33095947

RESUMO

BACKGROUND: Primary cilia influence cell function and tissue development. Ciliary signaling is mediated by two intraflagellar transport (IFT) protein complexes, IFT-A and IFT-B. The IFT-A complex is responsible for retrograde transport, and IFT140 is a core protein in the A complex. Mutations in IFT140 cause a variety of skeletal disorders. However, the expression and role of IFT140 during bone development remain unclear. In this study, to further explore the potential role of IFT140 in osteogenesis, we used cell lineage tracing and conditional knockout to analyze the distribution and function of IFT140-positive cells during bone formation. RESULTS: In newborn Ift140-creER; R26RtdTomato mice, IFT140-positive cells were mainly located in the medullary cavity and then migrated to and differentiated on the surface of trabecular and cortical bone. In contrast, the number of IFT140-positive cells significantly decreased in the adult stage, and these cells were only located in the bone marrow cavity for a short time. In Osx-cre; Ift140flox/flox mice, the loss of IFT140 in preosteoblasts caused bone loss in the trabecular bone area at 10 weeks. CONCLUSION: The results revealed that IFT140-positive cells mainly contribute to the early stage of bone formation.


Assuntos
Proteínas de Transporte/fisiologia , Osteogênese , Animais , Animais Recém-Nascidos , Doenças do Desenvolvimento Ósseo/genética , Linhagem da Célula , Camundongos Knockout
2.
Int J Oral Sci ; 15(1): 22, 2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268650

RESUMO

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.


Assuntos
Proteínas Hedgehog , Receptores Acoplados a Proteínas G , Camundongos , Animais , Proteínas Hedgehog/genética , Receptores Acoplados a Proteínas G/metabolismo , Cílios/metabolismo , Cartilagem/metabolismo , Regeneração
3.
Int J Oral Sci ; 14(1): 5, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078971

RESUMO

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1+ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1+ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1+ cells in PDL cells. The behavior of PRX1+ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1+ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1+ cells; during transplanted teeth PDL reconstruction, PRX1+ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1+ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.


Assuntos
Células-Tronco Mesenquimais , Ligamento Periodontal , Animais , Diferenciação Celular , Camundongos , Dente Molar , Osteogênese/fisiologia
4.
J Histochem Cytochem ; 67(8): 601-611, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31034313

RESUMO

Primary cilia have a pivotal role in bone development and the dysfunctions of primary cilia cause skeletal ciliopathies. Intraflagellar transport (IFT) proteins are conserved mediators of cilium signaling. IFT sub-complex A is known to regulate retrograde IFT in the cilium. As a core protein of IFT complex A, IFT140 has been shown to have a relationship with serious skeletal ciliopathies caused in humans. However, the effects and mechanisms of IFT140 in bone formation have not been systematically disclosed. To further investigate the potential role of IFT140 in osteogenesis, we established a mouse model by conditional deletion of IFT140 in pre-osteoblasts. The adult knock-out mice exhibited dwarf phenotypes, such as short bone length, less bone mass, and decreased bone mineral apposition rate. In addition, by IFT140 deletion, the expressions of several osteoblastic markers were decreased and loss of bone became severe with aging. These results suggest that cilia gene Ift140 is essential in bone development.


Assuntos
Osso e Ossos/fisiologia , Proteínas de Transporte/metabolismo , Osteogênese , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Animais , Proteínas de Transporte/genética , Cílios/metabolismo , Feminino , Técnicas de Inativação de Genes , Lâmina de Crescimento/metabolismo , Lâmina de Crescimento/fisiologia , Camundongos , Fenótipo
5.
Front Med ; 13(5): 575-589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31065929

RESUMO

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.


Assuntos
Condrogênese , Proteínas da Matriz Extracelular/genética , Consolidação da Fratura , Glicosilação , Animais , Cartilagem/metabolismo , Condrócitos/metabolismo , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/química , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos , Microtomografia por Raio-X
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