The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice

Abstract

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20–24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

Characterization and assessment of lung and bone marrow derived endothelial cells and their bone regenerative potential

“…All tissue isolation was performed in a sterile environment. LECs and BMECs were isolated from neonatal mice (2-6 days of age) as described previously ( 4 , 32 , 33 ).…”

“…Tube formation was assessed by Matrigel tube formation assay as previously described ( 32 , 34 ). Matrigel basement membrane matrix (Corning ® , Corning, NY) was polymerized in 96-well plates (50μl/well) at 37°C and 5% CO 2 for 45 minutes.…”

PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action

“…SRT1720 is a synthetic compound that activates SIRT1(( Minor et al, 2011 ; Svensson et al, 2015 )) and has been implicated in the regulation of neurogenesis ( Iwata et al, 2020 ) and angiogenesis ( Dadwal et al, 2021 ) through activation of SIRT1. It has also been shown that SRT1720 can reduce pain due to bone cancer ( Li et al, 2019 ) and intervertebral disc degeneration ( Zhang et al, 2020 ) by activating SIRT1.…”