Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3.

Autophagy receptor OPTN (optineurin) regulates mesenchymal stem cell fate and bone-fat balance during aging by clearing FABP3. Autophagy. 2020 Nov 04;:1-17 Authors: Liu ZZ, Hong CG, Hu WB, Chen ML, Duan R, Li HM, Yue T, Cao J, Wang ZX, Chen CY, Hu XK, Wu B, Liu HM, Tan YJ, Liu JH, Luo ZW, Zhang Y, Rao SS, Luo MJ, Yin H, Wang YY, Xia K, Xu L, Tang SY, Hu RG, Xie H Abstract Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn- / - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn- / - mice or infecting optn- / - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of ...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research