Interaction of TGFβ and BMP Signaling Pathways during Chondrogenesis

TGFβ and BMP signaling pathways exhibit antagonistic activities during the development of many tissues. Although the crosstalk between BMP and TGFβ signaling pathways is well established in bone development, the relationship between these two pathways is less well defined during cartilage development and postnatal homeostasis. We generated hypomorphic mouse models of cartilage-specific loss of BMP and TGFβ signaling to assess the interaction of these pathways in postnatal growth plate homeostasis. We further used the chondrogenic ATDC5 cell line to test effects of BMP and TGFβ signaling on each other's downstream targets. We found that conditional deletion of Smad1 in chondrocytes resulted in a shortening of the growth plate. The addition of Smad5 haploinsufficiency led to a more severe phenotype with shorter prehypertrophic and hypertrophic zones and decreased chondrocyte proliferation. The opposite growth plate phenotype was observed in a transgenic mouse model of decreased chondrocytic TGFβ signaling that was generated by expressing a dominant negative form of the TGFβ receptor I (ΔTβRI) in cartilage. Histological analysis demonstrated elongated growth plates with enhanced Ihh expression, as well as an increased proliferation rate with altered production of extracellular matrix components. In contrast, in chondrogenic ATDC5 cells, TGFβ was able to enhance BMP signaling, while BMP2 significantly reduces levels of TGF signaling. In summary, our data demonstrate that during endochondral ossification, BMP and TGFβ signaling can have antagonistic effects on chondrocyte proliferation and differentiation in vivo. We also found evidence of direct interaction between the two signaling pathways in a cell model of chondrogenesis in vitro

Association between Grape Yeast Communities and the Vineyard Ecosystems

The grape yeast biota from several wine-producing areas, with distinct soil types and grapevine training systems, was assessed on five islands of Azores Archipelago, and differences in yeast communities composition associated with the geographic origin of the grapes were explored. Fifty-seven grape samples belonging to the Vitis vinifera grapevine cultivars Verdelho dos Acores (Verdelho), Arinto da Terceira (Arinto) and Terrantez do Pico (Terrantez) were collected in two consecutive years and 40 spontaneous fermentations were achieved. A total of 1710 yeast isolates were obtained from freshly crushed grapes and 1200 from final stage of fermentations. Twenty-eight species were identified, Hanseniaspura uvarum, Pichia terricola and Metschnikowia pulcherrima being the three most representative species isolated. Candida carpophila was encountered for the first time as an inhabitant of grape or wine-associated environments. In both sampling years, a higher proportion of H. uvarum in fresh grapes from Verdelho cultivar was observed, in comparison with Arinto cultivar. Qualitatively significant differences were found among yeast communities from several locations on five islands of the Archipelago, particularly in locations with distinctive agro-ecological compositions. Our results are in agreement with the statement that grape-associated microbial biogeography is non-randomly associated with interactions of climate, soil, cultivar, and vine training systems in vineyard ecosystems. Our observations strongly support a possible linkage between grape yeast and wine typicality, reinforcing the statement that different viti-cultural terroirs harbor distinctive yeast biota, in particular in vineyards with very distinctive environmental conditions.Joao Drumonde Neves is the recipient of a fellowship of the Azorean Government (M321/006/F/2008) and PROEMPREGO. This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalizacao (POCI), and by national funds through FCT by the projects FCOMP-01-0124-008775, PTDC/AGR-ALI/103392/2008 and PTDC/AGR-ALI/121062/2010.info:eu-repo/semantics/publishedVersio

CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes

The matricellular protein CCN2 (Connective Tissue Growth Factor; CTGF) is an essential mediator of ECM composition, as revealed through analysis of Ccn2 deficient mice. These die at birth due to complications arising from impaired endochondral ossification. However, the mechanism(s) by which CCN2 mediates its effects in cartilage are unclear. We investigated these mechanisms using Ccn2−/− chondrocytes. Expression of type II collagen and aggrecan were decreased in Ccn2−/− chondrocytes, confirming a defect in ECM production. Ccn2−/− chondrocytes also exhibited impaired DNA synthesis and reduced adhesion to fibronectin. This latter defect is associated with decreased expression of α5 integrin. Moreover, CCN2 can bind to integrin α5β1 in chondrocytes and can stimulate increased expression of integrin α5. Consistent with an essential role for CCN2 as a ligand for integrins, immunofluorescence and Western blot analysis revealed that levels of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 phosphorylation were reduced in Ccn2−/− chondrocytes. These findings argue that CCN2 exerts major effects in chondrocytes through its ability to (1) regulate ECM production and integrin α5 expression, (2) engage integrins and (3) activate integrin-mediated signaling pathways

Bruxismo na infância: um sinal de alerta para odontopediatras e pediatras Childhood bruxism: a warning sign to pediatric dentists and pediatricians

OBJETIVO: Apresentar uma revisão de literatura sobre o bruxismo na infância, abordando os fatores etiológicos, as características clínicas, os sinais e sintomas, a importância do diagnóstico por parte dos pediatras e odontopediatras e o tratamento multidisciplinar desta condição parafuncional. FONTES DE DADOS: Foram selecionados os artigos mais relevantes sobre o tema publicados desde 1907 até 2007, com pesquisa realizada no Medline, na Bibliografia Brasileira de Odontologia (BBO) e em livros de Odontologia. SÍNTESE DOS DADOS: O bruxismo é definido como um hábito não funcional do sistema mastigatório, caracterizado pelo ato de ranger ou apertar os dentes, podendo ocorrer durante o dia e durante o sono. A etiologia é multifatorial e a literatura sugere vários fatores associados: dentário, fisiológico, psicológico e neurológico. As forças exercidas pelo bruxismo podem provocar distúrbios em diferentes graus nos dentes e nos tecidos de suporte, na musculatura e na articulação têmporo-mandibular. O sinal mais comum é o desgaste nas faces incisais dos dentes anteriores e oclusais nos posteriores, além de mobilidade e hipersensibilidade dentárias, fratura de cúspides e restaurações e hipertonicidade dos músculos mastigatórios. CONCLUSÃO: O conhecimento dos fatores etiológicos e das características clínicas do bruxismo na infância é fundamental para que o diagnóstico seja precoce, permitindo que pediatras, odontopediatras e psicólogos possam estabelecer um tratamento multidisciplinar e favoreçam o desenvolvimento integral da criança para a promoção de saúde e bem-estar individual.<br>OBJECTIVE: To present a review of literature on childhood bruxism, including etiological factors, clinical characteristics, signs and symptoms, the importance of the diagnosis by pediatric dentists and pediatricians and the multidisciplinary management of this parafunctional condition. DATA SOURCE: The most relevant articles published on the subject from 1907 to 2007 were selected, from Medline and Brazilian Bibliography on Odontology databases as well as dentistry books. DATA SYNTHESIS: Bruxism is defined as a non-functional habit of the stomatognatic system, characterized by the act of grinding or squeezing the teeth, with occurrences during the day or sleep. The etiology is multifactorial with contribution of several factors (dental, physiological, psychological and neurological variables). The forces produced by bruxism can harm the teeth, their supporting tissues, muscles and temporomandibular articulation. Common clinical signs are: attrition on the incisal faces of the anterior teeth and occlusal faces in the posterior teeth, as well as dental hypermobility and hypersensibility, cusp and restoration fracture and muscle hypertonicity. CONCLUSIONS: The knowledge on the etiological factors and the clinical characteristics of childhood bruxism is important to establish early diagnosis and treatment, with a multidisciplinary approach that should include pediatricians, pediatric dentists and psychologists in order to provide adequate infant development focused on health promotion and individual well-being