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

• Published in: Cell and tissue research Vol. 386; no. 2; pp. 335 - 347
• Main Authors: Souza, Alann Thaffarell Portilho, Lopes, Helena Bacha, Oliveira, Fabiola Singaretti, Weffort, Denise, Freitas, Gileade Pereira, Adolpho, Leticia Faustino, Fernandes, Roger Rodrigo, Rosa, Adalberto Luiz, Beloti, Marcio Mateus
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2021; Springer; Springer Nature B.V
• Subjects: 3T3 Cells; Agrin; Agrin - analysis; Agrin - genetics; Animals; Biomedical and Life Sciences; Biomedicine; Bone morphogenetic proteins; Cell Differentiation; Cells, Cultured; Chondrocytes; Chondrogenesis; Dystroglycan; Extracellular matrix; Gene Expression Regulation; Genes; Human Genetics; Humans; low density lipoprotein; Low density lipoproteins; Matrix protein; Mice; Mice, Inbred C57BL; Molecular Medicine; Osteoblastogenesis; Osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; Osteogenesis; Proteins; Proteomics; Receptor density; Regular Article; Signal transduction; therapeutics; Wnt protein; Osteoblast; Bone; BMP; Wnt; Agrin
• ISSN: 0302-766X; 1432-0878; 1432-0878
• DOI: 10.1007/s00441-021-03494-9

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 α-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.