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https://hdl.handle.net/10316/110996
Title: | The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice | Authors: | Warren, Aaron Porter, Ryan M Reyes-Castro, Olivia Ali, Md Mohsin Carvalho, Adriana Marques Kim, Ha-Neui Gatrell, Landon B Schipani, Ernestina Nookaew, Intawat O'Brien, Charles A. Morello, Roy Almeida, Maria |
Issue Date: | 17-Jun-2023 | Publisher: | Springer Nature | Project: | US National Institutes of Health R01AR056679 US National Institutes of Health R01AG068449 US National Institutes of Health P20GM125503 UAMS Bone and Joint Initiative |
Serial title, monograph or event: | Nature Communications | Volume: | 14 | Issue: | 1 | Abstract: | NAD is an essential co-factor for cellular energy metabolism and multiple other processes. Systemic NAD+ deficiency has been implicated in skeletal deformities during development in both humans and mice. NAD levels are maintained by multiple synthetic pathways but which ones are important in bone forming cells is unknown. Here, we generate mice with deletion of Nicotinamide Phosphoribosyltransferase (Nampt), a critical enzyme in the NAD salvage pathway, in all mesenchymal lineage cells of the limbs. At birth, NamptΔPrx1 exhibit dramatic limb shortening due to death of growth plate chondrocytes. Administration of the NAD precursor nicotinamide riboside during pregnancy prevents the majority of in utero defects. Depletion of NAD post-birth also promotes chondrocyte death, preventing further endochondral ossification and joint development. In contrast, osteoblast formation still occurs in knockout mice, in line with distinctly different microenvironments and reliance on redox reactions between chondrocytes and osteoblasts. These findings define a critical role for cell-autonomous NAD homeostasis during endochondral bone formation. | URI: | https://hdl.handle.net/10316/110996 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-023-39392-7 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice.pdf | 12.73 MB | Adobe PDF | View/Open |
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