Article ; Online: FGFR regulator Memo1 is dispensable for FGF23 expression by osteoblasts during folic acid-driven kidney injury.
2023 Volume 11, Issue 6, Page(s) e15650
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Female ; Humans ; Male ; Mice ; Acute Kidney Injury/metabolism ; Bone Diseases/metabolism ; Fibroblast Growth Factors/metabolism ; Folic Acid/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Kidney/metabolism ; Osteoblasts/metabolism ; X-Ray Microtomography |
| Chemical Substances | Fibroblast Growth Factors (62031-54-3) ; Folic Acid (935E97BOY8) ; Intracellular Signaling Peptides and Proteins ; Memo1 protein, mouse |
| Language | English |
| Publishing date | 2023-03-24 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2724325-4 |
| ISSN | 2051-817X ; 2051-817X |
| ISSN (online) | 2051-817X |
| ISSN | 2051-817X |
| DOI | 10.14814/phy2.15650 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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