FGFR regulator Memo1 is dispensable for FGF23 expression by osteoblasts during folic acid-driven kidney injury.

Bartos, Katalin; Moor, Matthias B (2023). FGFR regulator Memo1 is dispensable for FGF23 expression by osteoblasts during folic acid-driven kidney injury. Physiological reports, 11(6), e15650. The American Physiological Society 10.14814/phy2.15650

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Loss of the mediator Of cell motility 1 (Memo1) in mice caused kidney disease and a bone disease with diminished osteoblast and osteoclast biomarkers in serum, resembling alterations occurring in adynamic bone disease in humans with chronic kidney disease or in Klotho-deficient mice. Here, we investigated whether Memo1 expression in osteoblasts is required for normal bone structure and FGF23 expression. We deleted Memo1 in the osteoblast-osteocyte lineage in Memo fl/fl mice using a Cre under Col1a1 promotor to obtain osteoblast-specific knockout (obKO) mice. We studied organs by micro-computed tomography, qPCR, and western blot. We challenged mice with folic acid for acute kidney injury (AKI) and analyzed organs. Memo obKO were viable without changes in gross anatomy, serum electrolytes, or circulating FGF23 concentrations compared to controls. Memo1 expression was blunted in bones of Memo obKO, whereas it remained unchanged in other organs. Micro-CT revealed no differences between genotypes in bone structure of vertebrae, femur, and tibia. During AKI, Fgf23 expression in calvaria, and renal transcriptional changes were comparable between genotypes. However, renal injury marker expression, circulating FGF23, and parathyroid hormone revealed a sex difference with more severely affected females than males of either genotype. The present data imply that Memo1 in osteoblasts is dispensable for bone structure and expression of Fgf23. Moreover, we found evidence of potential sex differences in murine folic acid nephropathy similar to other experimental models of renal injury that are important to consider when using this experimental model of renal injury.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Bartos, Katalin, Moor, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2051-817X

Publisher:

The American Physiological Society

Language:

English

Submitter:

Pubmed Import

Date Deposited:

27 Mar 2023 10:29

Last Modified:

02 Apr 2023 02:14

Publisher DOI:

10.14814/phy2.15650

PubMed ID:

36967231

Uncontrolled Keywords:

FGF23 acute kidney injury folic acid osteoblast sex difference

BORIS DOI:

10.48350/180696

URI:

https://boris.unibe.ch/id/eprint/180696

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