C-C chemokine receptor type 6 modulates the biological function of osteoblastogenesis by altering the expression levels of Osterix and OPG/RANKL.
Biosci Trends
; 15(4): 240-248, 2021 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-34248133
ABSTRACT
Circulating inflammatory factors affect osteoblast and osteoclast formation and activity in osteoporosis. Estrogen affects the migration of Th17 cells via the C-C chemokine receptor type 6 (CCR6) and C-C chemokine ligand 20 (CCL20) signaling pathways to modulate bone metabolism; however, it is unclear whether and how CCR6 modulates bone homeostasis. In the present study, CCR6 knockout (CCR6-/-) mice were selected to investigate the effects of CCR6 in the regulation of homeostasis of osteoblasts and osteoclasts. Primary osteoblasts were isolated from the calvarium of newborn CCR6-/- or wild-type mice, followed by osteoblastic differentiation culture in vitro. CCR6 deletion reduced osteoblast activity in terms of alkaline phosphatase (ALP) activity and inhibited osteoblast mineralization according to the results of Alizarin Red S staining, whereas it did not affect the proliferation of osteoblasts. CCR6 deletion inhibited Osterix mRNA expression in osteoblasts during the late stage of mineralization in vitro, while it did not affect mRNA expression levels of runt-related transcription factor 2 (Runx2) and Collagen-1. The ratio of osteoprotegerin (OPG) /receptor activator of nuclear factor κ-Β ligand (RANKL) mRNA level in osteoblasts was decreased by CCR6 deficiency in the culture treated with 1,25(OH)2D3/PGE2, while there was no effect observed in the normal culture environment. The results provide novel insights, such as that CCR6 deletion suppresses osteoblast differentiation by downregulating the expression levels of the transcription factor Osterix, and indirectly promotes osteoclast production by increasing transcription of RANKL. This may be one of the mechanisms via which CCR6 deletion regulates bone metabolism.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligante RANK
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Osteoprotegerina
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Receptores CCR6
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Fator de Transcrição Sp7
Limite:
Animals
Idioma:
En
Revista:
Biosci Trends
Assunto da revista:
BIOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China