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

Autor: Souza ATP; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Lopes HB; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Oliveira FS; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Weffort D; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Freitas GP; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Adolpho LF; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Fernandes RR; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Rosa AL; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil., Beloti MM; Bone Research Lab, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. mmbeloti@usp.br.
Jazyk: angličtina
Zdroj: Cell and tissue research [Cell Tissue Res] 2021 Nov; Vol. 386 (2), pp. 335-347. Date of Electronic Publication: 2021 Jul 05.
DOI: 10.1007/s00441-021-03494-9
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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