The extracellular matrix protein Agrin is expressed by osteoblasts and contributes to their differentiation

Autor(es)

Souza, Alann Thaffarell Portilho ^[1] ; Lopes, Helena Bacha ^[1] ; Oliveira, Fabiola Singaretti ^[1] ; Weffort, Denise ^[1] ; Freitas, Gileade Pereira ^[1] ; Adolpho, Leticia Faustino ^[1] ; Fernandes, Roger Rodrigo ^[1] ; Rosa, Adalberto Luiz ^[1] ; Beloti, Marcio Mateus ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Dent Ribeirao Preto, Bone Res Lab, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cell and Tissue Research; v. 386, n. 2 JUL 2021.
• Citações Web of Science: 0

Resumo

The extracellular matrix protein Agrin has been detected in chondrocytes and endosteal osteoblasts but its function in osteoblast differentiation has not been investigated yet. Thus, it is possible that Agrin contributes to osteoblast differentiation and, due to Agrin and wingless-related integration site (Wnt) sharing the same receptor, transmembrane low-density lipoprotein receptor-related protein 4 (Lrp4), and the crosstalk between Wnt and bone morphogenetic protein (BMP) signalling, both pathways could be involved in this Agrin-mediated osteoblast differentiation. Confirming this, Agrin and its receptors Lrp4 and alpha-dystroglycan (Dag1) were expressed during differentiation of osteoblasts from three different sources. Moreover, the disruption of Agrin impaired the expression of its receptors and osteoblast differentiation, and the treatment with recombinant Agrin slightly increase this process. In addition, whilst Agrin knockdown downregulated the expression of genes related to Wnt and BMP signalling pathways, the addition of Agrin had no effect on these genes. Altogether, these data uncover the contribution of Agrin to osteoblast differentiation and suggest that, at least in part, an Agrin-Wnt-BMP circuit is involved in this process. This makes Agrin a candidate as target for developing new therapeutic strategies to treat bone-related diseases and injuries. (AU)

• Processo FAPESP: 16/14171-0 - Papel das Vias de Sinalização de Wnt no Potencial Osteogênico de Superfície de Titânio com Nanotopografia
• Beneficiário: Márcio Mateus Beloti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/20349-9 - Análise da expressão da proteína de matriz extracelular Agrin no processo de diferenciação osteoblástica
• Beneficiário: Denise Weffort
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica