ESPE Abstracts (2021) 94 P1-59

ESPE2021 ePoster Category 1 Bone B (10 abstracts)

Cartilage -specific knockout of SIRT1 significantly reduces bone quality and catch-up growth efficiency

Biana Shtaif 1 , Meytal Bar-Maisels 2 , Yankel Gabet 3 , Sahar Hiram-Bab 1 , Michal Yackobovitch-Gavan 2 , Moshe Phillip 1,2 & Galia Gat-Yablonski 1,2

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1Tel Aviv University, Tel Aviv, Israel; 2Schneider Children’s Medical Center, Petach Tikva, Israel; 3Tel Aviv University, Tel Aviv, Israel


Background: Spontaneous catch-up (CU) growth occurs when a growth-restricting factor is resolved. However, its efficiency is sometimes inadequate and growth deficits remain permanent. The therapeutic toolbox for short stature is currently very limited. Our previous studies using a nutrition-induced CU growth model showed that the level of sirtuin-1 (SIRT1) was significantly increased in food-restricted animals and decreased during CU growth.

Aim: This study sought to investigate the role of SIRT1 in modulating the response of the epiphyseal growth plate (EGP) to nutritional manipulation.

Method: Heterozygous collagen type II-specific Sirt1 knockout (CKO) mice were tested for response to our CU growth model consisting of a period of food restriction followed by re-feeding.

Results: The transgenic CKO mice weighed more than the control (CTL) mice, their EGP was higher and less organized, specifically at the resting and proliferative zones, leading to shorter bones. Ablation of Sirt1 in the chondrocytes was found to have a dramatic effect on bone mineralization on micro-CT analysis. The CKO mice were less responsive to the nutritional manipulation, and their CU growth was less efficient. They remained shorter than the CTL mice who corrected the food restriction-induced growth deficit during the re-feeding period.

Conclusions: Sirt1 appears to be important for normal regulation of the EGP. In its absence, the EGP is less organized and CU growth is less efficient. These results suggest that SIRT1 may serve as a novel therapeutic target for short stature.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

Online,
22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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