Cartilage -specific knockout of Sirt1 significantly reduces bone quality and catch-up growth efficiency

Shtaif, Biana; Bar-Maisels, Meytal; Gabet, Yankel; Hiram‐Bab, Sahar; Yackobovitch‐Gavan, Michal; Phillip, Moshe; Gat-Yablonski, Galia

doi:10.1016/j.bone.2020.115468

Cited by 10 publications

(16 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We studied nutritional-induced catch-up growth (CUG) using a model consisting of food restriction followed by refeeding. SIRT1 was among the few proteins that was increased in EGPs of food-restricted rats (2). Additionally, we showed that miR-140 and miR-22 were reduced at the EGP by food restriction, and their mutual target, SIRT1, showed a subsequent increase (1).…”

mentioning

confidence: 65%

“…It interacts and deacetylates histones and non-histone proteins such as p53, E2F1, NF-kB, and FOXO (4,5) and through them affects cell proliferation, senescence, autophagy, stress responses, and apoptosis. SIRT1 has been shown to have a substantial role in longevity (6), response to food restriction (1,7), and linear growth (1,2).…”

mentioning

confidence: 99%

“…Additionally, we showed that miR-140 and miR-22 were reduced at the EGP by food restriction, and their mutual target, SIRT1, showed a subsequent increase (1). Next, we knocked out Sirt1 expression using a collagen-type II-specific Cre-Lox system (2), and investigated its role in nutrition-induced CUG.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Anxiety and Cognition in Cre- Collagen Type II Sirt1 K/O Male Mice

Shtaif

Hornfeld²,

Yackobovitch‐Gavan

et al. 2021

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

IntroductionUsing transgenic collagen type II-specific Sirt1 knockout (CKO) mice we studied the role of Sirt1 in nutritional induced catch up growth (CUG) and we found that these mice have a less organized growth plate and reduced efficiency of CUG. In addition, we noted that they weigh more than control (CTL) mice. Studying the reason for the increased weigh, we found differences in activity and brain function.MethodsSeveral tests for behavior and activity were used: open field; elevated plus maze, Morris water maze, and home cage running wheels. The level of Glu- osteocalcin, known to connect bone and brain function, was measured by Elisa; brain Sirt1 was analyzed by western blot.ResultsWe found that CKO mice had increased anxiety, with less spatial memory, learning capabilities and reduced activity in their home cages. No significant differences were found between CKO and CTL mice in Glu- osteocalcin levels; nor in the level of brain SIRT1.Discussion/ConclusionUsing transgenic collagen type II-specific Sirt1 knockout (CKO) mice we found a close connection between linear growth and brain function. Using a collagen type II derived system we affected a central regulatory mechanism leading to hypo activity, increased anxiety, and slower learning, without affecting circadian period. As children with idiopathic short stature are more likely to have lower IQ, with substantial deficits in working memory than healthy controls, the results of the current study suggest that SIRT1 may be the underlying factor connecting growth and brain function.

show abstract

mentioning

confidence: 65%

mentioning

confidence: 99%

See 1 more Smart Citation

Anxiety and Cognition in Cre- Collagen Type II Sirt1 K/O Male Mice

Shtaif

Hornfeld²,

Yackobovitch‐Gavan

et al. 2021

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…These findings were consistent with reduced levels of SIRT1 measured in human osteoarthritis (OA) cartilage (Fujita et al, 2011; Takayama et al, 2009), suggesting a potential protective role of SIRT1 in chondrocytes, which was further evidenced by the accelerated development of OA in mice lacking SIRT1 in chondrocyte (Matsuzaki et al, 2014). However, a recent finding demonstrated an increased ratio of proliferative‐to‐hypertrophic zone following SIRT1 deletion in chondrocyte, suggesting SIRT1 inhibits chondrocyte proliferation (Shtaif et al, 2020). Possible reason for the discrepancy could be due to the differences in the genetic models, which requires further investigation.…”

Section: Sirtuins In Bone Biologymentioning

confidence: 99%

“…Possible reason for the discrepancy could be due to the differences in the genetic models, which requires further investigation. In addition to its role in chondrogenesis, the absence of SIRT1 in chondrocytes also resulted in decreased trabecular and cortical bone mineralization, which was attributed to the disorganized epiphyseal growth plate in chondrocyte‐specific KO mice (Shtaif et al, 2020).…”

Section: Sirtuins In Bone Biologymentioning

confidence: 99%

Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis

Cheng

Jiang

et al. 2021

Aging Cell

View full text Add to dashboard Cite

The decline in bone mass and bone strength and musculoskeletal problems associated with aging constitute a major challenge for affected individuals and the healthcare system globally. Sirtuins 1‐7 (SIRT1‐SIRT7) are a family of nicotinamide adenine dinucleotide‐dependent deacetylases with remarkable abilities to promote longevity and counteract age‐related diseases. Sirtuin knockout and transgenic models have provided novel insights into the function and signaling of these proteins in bone homeostasis. Studies have revealed that sirtuins play a critical role in normal skeletal development and homeostasis through their direct action on bone cells and that their dysregulation might contribute to different bone diseases. Preclinical studies have demonstrated that mice treated with sirtuin agonists show protection against age‐related, postmenopausal, and immobilization‐induced osteoporosis. These findings suggest that sirtuins could be potential targets for the modulation of the imbalance in bone remodeling and treatment of osteoporosis and other bone disorders. The aim of this review was to provide a comprehensive updated review of the current knowledge on sirtuin biology, focusing specifically on their roles in bone homeostasis and osteoporosis, and potential pharmacological interventions targeting sirtuins for the treatment of osteoporosis.

show abstract

Targeting Endogenous Hydrogen Peroxide at Bone Defects Promotes Bone Repair

Han

et al. 2021

Adv Funct Materials

View full text Add to dashboard Cite

Reactive oxygen species (ROS) plays a critical role in tissue repair, including bone. Therefore, detecting and regulating ROS is essential for monitoring and facilitating bone repair. In this study, for the first time, the spatiotemporal profile of ROS, represented by hydrogen peroxide (H2O2), in the bone injury microenvironment using photoacoustic imaging technique is visualized. The ROS levels significantly increase upon bone injury, peak at a certain stage of bone healing, and then gradually decrease toward baseline level. To regulate ROS in the bone injury microenvironment, the use of hollow manganese dioxide nanoparticles (hMNPs), which are able to decompose H2O2 and generate oxygen is explored. In vitro, hMNPs eliminate intracellular ROS to protect cells from oxidative damage and facilitate cell growth by releasing oxygen. In vivo, composite hydrogels containing gelatin methacryloyl (GelMA) and hMNPs (hMNP/GelMA) release oxygen and bone morphogenetic protein‐2 (BMP‐2)‐associated peptide in an “on‐demand” fashion in response to bone microenvironmental ROS change. Applying hMNP/GelMA composite hydrogels loaded with BMP‐2‐associated peptide (BhMNP/GelMA) significantly enhances bone formation in a rat critical‐sized calvarial defect. Together, findings from this study imply that the visualization and regulation of ROS such as H2O2 may be a novel strategy for diagnosing and treating bone defects.

show abstract

Cartilage -specific knockout of Sirt1 significantly reduces bone quality and catch-up growth efficiency

Cited by 10 publications

References 57 publications

Anxiety and Cognition in Cre- Collagen Type II Sirt1 K/O Male Mice

Anxiety and Cognition in Cre- Collagen Type II Sirt1 K/O Male Mice

Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis

Targeting Endogenous Hydrogen Peroxide at Bone Defects Promotes Bone Repair

Contact Info

Product

Resources

About