Your browser doesn't support javascript.
loading
NFATc1 Is Required for Vitamin D- and Phosphate-Mediated Regulation of Osteocyte Lacuno-Canalicular Remodeling.
Jagga, Supriya; Hughes, Ashleigh; Manoochehri Arash, Niusha; Sorsby, Melissa; Brooks, Daniel J; Divieti Pajevic, Paola; Liu, Eva S.
Afiliação
  • Jagga S; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Hughes A; Harvard Medical School, Boston, MA 02115, USA.
  • Manoochehri Arash N; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Sorsby M; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Brooks DJ; Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Divieti Pajevic P; Harvard Medical School, Boston, MA 02115, USA.
  • Liu ES; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Endocrinology ; 165(8)2024 Jul 01.
Article em En | MEDLINE | ID: mdl-39024412
ABSTRACT
Osteocytes are embedded in lacunae and connected by canaliculi (lacuno-canalicular network, LCN). Bones from mice with X-linked hypophosphatemia (Hyp), which have impaired production of 1,25 dihydroxyvitamin D (1,25D) and hypophosphatemia, have abnormal LCN structure that is improved by treatment with 1,25D or an anti-FGF23 targeting antibody, supporting roles for 1,25D and phosphate in regulating LCN remodeling. Bones from mice lacking the vitamin D receptor (VDR) in osteocytes (Vdrf/f;Dmp1Cre+) and mice lacking the sodium phosphate transporter 2a (Npt2aKO), which have low serum phosphate with high serum 1,25D, have impaired LCN organization, demonstrating that osteocyte-specific actions of 1,25D and hypophosphatemia regulate LCN remodeling. In osteoclasts, nuclear factor of activated T cells cytoplasmic 1 (NFATc1) is critical for stimulating bone resorption. Since osteocytes also resorb matrix, we hypothesize that NFATc1 plays a role in 1,25D and phosphate-mediated LCN remodeling. Consistent with this, 1,25D and phosphate suppress Nfatc1 mRNA expression in IDG-SW3 osteocytes, and knockdown of Nfatc1 expression in IDG-SW3 cells blocks 1,25D- and phosphate-mediated suppression of matrix resorption gene expression and 1,25D- and phosphate-mediated suppression of RANKL-induced acidification of the osteocyte microenvironment. To determine the role of NFATc1 in 1,25D- and phosphate-mediated LCN remodeling in vivo, histomorphometric analyses of tibiae from mice lacking osteocyte-specific Nfatc1 in Vdrf/f;Dmp1Cre+ and Npt2aKO mice were performed, demonstrating that bones from these mice have decreased lacunar size and expression of matrix resorption genes, and improved canalicular structure compared to Vdrf/f;Dmp1Cre+ and Npt2aKO control. This study demonstrates that NFATc1 is necessary for 1,25D- and phosphate-mediated regulation of LCN remodeling.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteócitos / Fosfatos / Vitamina D / Remodelação Óssea / Fatores de Transcrição NFATC / Fator de Crescimento de Fibroblastos 23 Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Osteócitos / Fosfatos / Vitamina D / Remodelação Óssea / Fatores de Transcrição NFATC / Fator de Crescimento de Fibroblastos 23 Idioma: En Ano de publicação: 2024 Tipo de documento: Article