Fu, Shijian, Johnson, Kirsty A, Winstanley-Zarach, Phaedra, Ersoy, Ufuk, Adlmanninger, Elena, McDermott, Benjamin T, Keenan, Craig, Vasilaki, Aphrodite, Kanakis, Ioannis, Milner, Peter I et al (show 5 more authors)
(2025)
Loss of the RNA Binding Protein HuR in Early Murine Limb Mesenchyme Does Not Affect Development but Leads to Impaired Bone Homeostasis in Adulthood.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39 (22).
e71222-.
ISSN 0892-6638, 1530-6860
Abstract
In this study, we examined how a critical posttranscriptional regulator, the RNA-binding protein HuR (gene name Elavl1), contributes to the development and maintenance of limb skeletal tissue. Using the Prx1-Cre knockout model, we examined the effect of germline knockout (Elavl1KO) and limb mesenchyme-specific knockout (MSC-Elavl1KO) of HuR on limb development. We found that Elavl1KO disrupted the development of the limb skeleton and was associated with a loss of signaling from the apical ectodermal ridge (AER). In contrast, MSC-Elavl1KO did not appear to affect skeletal development. Mature MSC-Elavl1KO mice appeared healthy, but their limb skeleton exhibited abnormal bone structure in both males and females at 2.5 months of age. Osteoblasts isolated from MSC-Elavl1KO mice exhibited lower expression of osteoblastic marker genes, and their ability to generate a mineralized matrix was markedly impaired. RNA-Seq analysis of these osteoblasts demonstrated that loss of HuR substantially influenced their transcriptome, affecting genes associated with a wide range of cellular processes. Finally, using siRNA knockdown in the human MG63 cell line, we identified that loss of HuR leads to increased mRNA turnover of the osteoblastic transcription factor Runx2. Overall, the study has demonstrated a critical role for HuR-mediated posttranscriptional control in skeletal development and homeostasis, but finds that its expression in mesenchyme-derived cells only becomes critical in mature skeletal tissue.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Extremities, Bone and Bones, Osteoblasts, Mesoderm, Animals, Mice, Knockout, Mice, Gene Expression Regulation, Developmental, Bone Development, Osteogenesis, Homeostasis, Female, Male, ELAV-Like Protein 1 |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff) Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Musculoskeletal & Ageing Science |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 20 Nov 2025 10:31 |
| Last Modified: | 25 Nov 2025 16:55 |
| DOI: | 10.1096/fj.202500780rr |
| Open Access URL: | https://faseb.onlinelibrary.wiley.com/doi/epdf/10.... |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3195523 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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