Scara3 regulates bone marrow mesenchymal stem cell fate switch between osteoblasts and adipocytes by promoting Foxo1.
Scara3 regulates bone marrow mesenchymal stem cell fate switch between osteoblasts and adipocytes by promoting Foxo1.
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Scara3通过促进Foxo1调节骨髓间充质干细胞在成骨细胞和脂肪细胞之间的命运转换
DOI：
10.1111/cpr.13095
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发表时间：
2021-08
影响因子：
8.5
通讯作者：
Peng H
中科院分区：
文献类型：
--
作者：
Chen P;Hu B;Xie LQ;Jiang TJ;Xia ZY;Peng H
A类清道夫受体3（Scara 3）参与脂肪形成。然而，Scara 3在骨髓间充质干细胞（BMSCs）成骨和成脂之间的转换中的作用仍然是难以捉摸的。基于GTEx数据库分析SCARA 3与成骨相关的相关性。通过qPCR、Western blot和细胞染色观察Scara 3对BMSCs成骨、成脂分化的影响。通过共表达分析、WB和免疫荧光验证Scara 3调节Foxo 1和自噬的机制。在体内，将Scara 3腺相关病毒注射到老年小鼠和卵巢切除（OVX）小鼠的骨髓内，其表型通过micro-CT、钙黄绿素双标记和免疫化学（HE和OCN染色）确认。 SCARA 3与成骨相关基因呈正相关。Scara 3的表达在脂肪形成过程中逐渐减少，但在骨形成过程中增加。此外，Scara 3的缺失有利于脂肪生成，而过表达Scara 3则以脂肪生成为代价显著增强了骨生成。Scara 3通过促进Foxo 1表达和自噬通量来控制细胞命运。在体内，Scara 3促进OVX小鼠的骨形成并减少骨髓脂肪积累。在老年小鼠中，Scara 3过表达也减轻了骨丢失。这项研究表明，Scara 3调节脂肪细胞和成骨细胞分化之间的转换，这代表了骨丢失和骨质疏松症的潜在治疗靶点。异常的自噬导致了骨质疏松症的发生，部分与骨髓间充质干细胞成骨分化的增加和成脂分化的减少有关。而Scara 3可以促进Foxo 1的表达和自噬通量，从而减轻骨丢失和骨髓脂肪组织堆积。
Scavenger receptor class A, member 3 (Scara3) was involved in adipogenesis. However, the effect of Scara3 on the switch between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) remains elusive. The correlations between SCARA3 with the osteogenic‐related were analysed based on the GTEx database. The effects of Scara3 on osteogenic or adipogenic differentiation of BMSCs were evaluated by qPCR, Western blot (WB) and cell staining. The mechanisms of Scara3 regulating Foxo1 and autophagy were validated by co‐expression analysis, WB and immunofluorescence. In vivo, Scara3 adeno‐associated virus was injected into intra‐bone marrow of the aged mice and ovariectomized (OVX) mice whose phenotypes were confirmed by micro‐CT, calcein double labelling and immunochemistry (HE and OCN staining). SCARA3 was positively correlated with osteogenic‐related genes. Scara3 expression gradually decreased during adipogenesis but increased during osteogenesis. Moreover, the deletion of Scara3 favoured adipogenesis over osteogenesis, whereas overexpression of Scara3 significantly enhanced the osteogenesis at the expense of adipogenesis. Mechanistically, Scara3 controlled the cell fate by promoting Foxo1 expression and autophagy flux. In vivo, Scara3 promoted bone formation and reduced bone marrow fat accumulation in OVX mice. In the aged mice, Scara3 overexpression alleviated bone loss as well. This study suggested that Scara3 regulated the switch between adipocyte and osteoblast differentiation, which represented a potential therapeutic target for bone loss and osteoporosis. Aberrant autophagy caused the pathogenesis of osteoporosis, partially associated with the increase of osteogenic differentiation and decrease of adipogenic differentiation in BMSCs. However, Scara3 can promote the Foxo1 expression and autophagy flux, thus alleviate the bone loss and bone marrow adipose tissue accumulation.
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影响因子：
29
作者：
Ambrogini E;Almeida M;Martin-Millan M;Paik JH;Depinho RA;Han L;Goellner J;Weinstein RS;Jilka RL;O'Brien CA;Manolagas SC
通讯作者：
Manolagas SC
清道夫受体A类成员3（Scara3）在多发性骨髓瘤的疾病进展和耐药性中。
影响因子：
2.7
作者：
Brown CO;Schibler J;Fitzgerald MP;Singh N;Salem K;Zhan F;Goel A
通讯作者：
Goel A
DOI：
10.1515/bjmg-2015-0081
发表时间：
2015-12-01
期刊：
Balkan journal of medical genetics : BJMG
影响因子：
--
作者：
Karachanak-Yankova S;Dimova R;Nikolova D;Nesheva D;Koprinarova M;Maslyankov S;Tafradjiska R;Gateva P;Velizarova M;Hammoudeh Z;Stoynev N;Toncheva D;Tankova T;Dimova I
通讯作者：
Dimova I
影响因子：
13.3
作者：
Nollet, Marie;Santucci-Darmanin, Sabine;Pierrefite-Carle, Valerie
通讯作者：
Pierrefite-Carle, Valerie
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B