Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis.

Chen, Taiqiu; Peng, Yan; Hu, Wenjun; Shi, Huihong; Li, Pengfei; Que, Yichen; Qiu, Jincheng; Qiu, Xianjian; Gao, Bo; Zhou, Hang; Chen, Yanbo; Zhu, Yuanxin; Li, Shaoguang; Liang, Anjing; Gao, Wenjie; Huang, Dongsheng

doi:10.21203/rs.3.rs-1285516/v1

Cited by 1 publication

(1 citation statement)

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“…In a group of postmenopausal women with low bone mass, irisin levels in the circulation closely correlated with bone mineral status and osteoporotic fracture risk [16], suggesting that irisin may act as a biochemical marker of bone mineral-related diseases. Further studies confirmed the potential effects of irisin on bone metabolism by indicating that irisin could not only prevent the inhibition of osteoblast differentiation under stimulated microgravity conditions but also enhance the osteogenic and chondrogenic differentiation of MSCs by modulating the Wnt/βcatenin signaling pathway [17][18][19]. However, the effect of irisin on cell injuries and ASC osteogenic differentiation under hyperglycemic conditions is not fully understood.…”

Section: Introductionmentioning

confidence: 94%

Irisin Promotes Osteogenesis by Modulating Oxidative Stress and Mitophagy through SIRT3 Signaling under Diabetic Conditions

Jian

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Advanced glycation end products (AGEs) accumulate in the bone tissue of patients with diabetes mellitus, resulting in oxidative stress, poor bone healing, or regeneration. Irisin, a novel exercise-induced myokine, is involved in the regulation of bone metabolism. However, the effects of irisin on adipose-derived stem cell (ASC) osteogenic differentiation and bone healing under diabetic conditions remain poorly understood. ASCs were obtained from inguinal fat of Sprague-Dawley rats and treated with different concentrations of AGEs and irisin. Cell proliferation, apoptosis, and osteogenic differentiation abilities of ASCs were detected. To explore the regulatory role of sirtuin 3 (SIRT3), ASCs were transfected with lentivirus-mediated SIRT3 overexpression or knockdown vectors. Next, we investigated mitochondrial functions, mitophagy, and mitochondrial biogenesis in different groups. Moreover, SOD2 acetylation and potential signaling pathways were assessed. Additionally, a diabetic rat model was used to evaluate the effect of irisin on bone healing in calvarial critical-sized defects (CSDs) in vivo. Our results showed that irisin incubation mitigated the inhibitory effects of AGEs on ASCs by increasing cell viability and promoting osteogenesis. Moreover, irisin modulated mitochondrial membrane potential, intracellular ROS levels, mitochondrial O2·− status, ATP generation, complex I and IV activities, mitophagy, and mitochondrial biogenesis via a SIRT3-mediated pathway under AGEs exposure. Furthermore, in calvarial CSDs of diabetic rats, transplantation of gels encapsulating irisin-pretreated ASCs along with irisin largely enhanced bone healing. These findings suggest that irisin attenuates AGE-induced ASC dysfunction through SIRT3-mediated maintenance of oxidative stress homeostasis and regulation of mitophagy and mitochondrial biogenesis. Thus, our studies shed new light on the role of irisin in promoting the ASC osteogenesis and targeting SIRT3 as a novel therapeutic intervention strategy for bone regeneration under diabetic conditions.

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