PMID- 34254370
OWN - NLM
STAT- MEDLINE
DCOM- 20210817
LR  - 20210817
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 54
IP  - 8
DP  - 2021 Aug
TI  - Scara3 regulates bone marrow mesenchymal stem cell fate switch between 
      osteoblasts and adipocytes by promoting Foxo1.
PG  - e13095
LID - 10.1111/cpr.13095 [doi]
LID - e13095
AB  - OBJECTIVES: 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. 
      MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 
      This study suggested that Scara3 regulated the switch between adipocyte and 
      osteoblast differentiation, which represented a potential therapeutic target for 
      bone loss and osteoporosis.
CI  - (c) 2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.
FAU - Chen, Peng
AU  - Chen P
AD  - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of 
      Central South University, Changsha, China.
AD  - Department of Orthopedic, Xiangya Hospital of Central South University, Changsha, 
      China.
FAU - Hu, Biao
AU  - Hu B
AD  - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of 
      Central South University, Changsha, China.
FAU - Xie, Ling-Qi
AU  - Xie LQ
AD  - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of 
      Central South University, Changsha, China.
FAU - Jiang, Tie-Jian
AU  - Jiang TJ
AD  - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of 
      Central South University, Changsha, China.
FAU - Xia, Zhu-Ying
AU  - Xia ZY
AD  - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of 
      Central South University, Changsha, China.
FAU - Peng, Hui
AU  - Peng H
AUID- ORCID: 0000-0002-7673-3919
AD  - Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of 
      Central South University, Changsha, China.
LA  - eng
GR  - 81770877/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20210712
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Foxo1 protein, mouse)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Scavenger Receptors, Class A)
SB  - IM
MH  - Adipocytes/*cytology/metabolism
MH  - Adipogenesis
MH  - Aging
MH  - Animals
MH  - Autophagy
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Female
MH  - Forkhead Box Protein O1/*metabolism
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteoblasts/*cytology/metabolism
MH  - Osteogenesis
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Scavenger Receptors, Class A/antagonists & inhibitors/genetics/*metabolism
PMC - PMC8349663
OTO - NOTNLM
OT  - Scara3
OT  - BMSCs
OT  - adipocytes
OT  - osteoblasts
OT  - osteoporosis
COIS- The authors declare that they have no competing interests.
EDAT- 2021/07/14 06:00
MHDA- 2021/08/18 06:00
PMCR- 2021/07/12
CRDT- 2021/07/13 06:45
PHST- 2021/06/25 00:00 [revised]
PHST- 2021/04/10 00:00 [received]
PHST- 2021/06/26 00:00 [accepted]
PHST- 2021/07/14 06:00 [pubmed]
PHST- 2021/08/18 06:00 [medline]
PHST- 2021/07/13 06:45 [entrez]
PHST- 2021/07/12 00:00 [pmc-release]
AID - CPR13095 [pii]
AID - 10.1111/cpr.13095 [doi]
PST - ppublish
SO  - Cell Prolif. 2021 Aug;54(8):e13095. doi: 10.1111/cpr.13095. Epub 2021 Jul 12.