| Autor: |
Stéphanie Fabre, Morgane Bourmaud, Guillaume Mabilleau, Ruben Goulet, Aude Couturier, Alexandre Dentel, Serge Picaud, Thomas Funck‐Brentano, Corinne Collet, Martine Cohen‐Solal |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
JBMR Plus, Vol 7, Iss 6, Pp n/a-n/a (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2473-4039 |
| DOI: |
10.1002/jbm4.10741 |
| Popis: |
ABSTRACT Early‐onset osteoporosis (EOOP) has been associated with several genes, including LRP5, coding for a coreceptor in the Wnt pathway. Variants in LRP5 were also described in osteoporosis pseudoglioma syndrome, combining severe osteoporosis and eye abnormalities. Genomewide‐association studies (GWAS) showed that LRP5 p.Val667Met (V667M) variant is associated with low bone mineral density (BMD) and increased fractures. However, despite association with a bone phenotype in humans and knockout mice, the impact of the variant in bone and eye remains to be investigated. Here, we aimed to evaluate the bone and ocular impact of the V667M variant. We recruited 11 patients carrying the V667M variant or other loss‐of‐function variants of LRP5 and generated an Lrp5V667M mutated mice. Patients had low lumbar and hip BMD Z‐score and altered bone microarchitecture evaluated by HR‐pQCT compared with an age‐matched reference population. Murine primary osteoblasts from Lrp5V667M mice showed lower differentiation capacity, alkaline phosphatase activity, and mineralization capacity in vitro. Ex vivo, mRNA expression of Osx, Col1, and osteocalcin was lower in Lrp5V667M bones than controls (all p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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