Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

Shu，Bing1,2,3; Zhao，Yongjian1,2,3; Zhao，Shitian1,2,3; Pan，Haobo4; Xie，Rong5; Yi，Dan4; Lu，Ke5; Yang，Junjie1,2,3; Xue，Chunchun1,2,3; Huang，Jian5; Wang，Jing1,3; Zhao，Dongfeng1,2,3; Xiao，Guozhi6; Wang，Yongjun1,2,3; Chen，Di4

2020-12-01

10.1038/s41413-020-0104-5

Bone Research   影响因子和分区

2095-4700

2095-6231

Axin1 is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined. In the present studies, we determined changes in postnatal bone growth by deletion of Axin1 in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1 mice and found that hypertrophic cartilage area was largely expanded in Axin1 KO mice. A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1 KO mice. Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased, demonstrated by decreased TRAP-positive cell numbers, associated with reduction of MMP9- and cathepsin K-positive cell numbers in Axin1 KO mice. OPG expression and the ratio of Opg to Rankl were significantly increased in osteoblasts of Axin1 KO mice. Osteoclast formation in primary bone marrow derived microphage (BMM) cells was significantly decreased when BMM cells were cultured with conditioned media (CM) collected from osteoblasts derived from Axin1 mice compared with BMM cells cultured with CM derived from WT mice. Thus, the loss of Axin1 in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation, leading to delayed bone growth in postnatal Axin1 KO mice.

SCI

英语

其他

National Natural Science Foundation of China (NSFC)[81991513][81973876][81673991][81730107][81603643][81672227] ; National Key R&D Program of China[2018YFC1704302] ; Program for Innovative Research Team in University, Ministry of Education of China[IRT1270] ; Program for Innovative Research Team, Ministry of Science and Technology of China[2015RA4002] ; Three Years Action to Accelerate the Development of Traditional Chinese Medicine Plan[ZY (2018-2020)-CCCX-3003] ; Frontier Science of CAS grant[QYZDB-SSW-JSC030]

Cell Biology

Cell & Tissue Engineering

WOS:000560192500001

NATURE PUBLISHING GROUP

2-s2.0-85089390221

Scopus

1.Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai,725 WanPing South Road,200032,China
2.Spine Institute,Shanghai Academy of Traditional Chinese Medicine,Shanghai,725 WanPing South Road,200032,China
3.Key Laboratory,Ministry of Education of China,Shanghai,725 WanPing South Road,200032,China
4.Research Center for Human Tissues and Organs Degeneration,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China
5.Department of Orthopedic Surgery,Rush University Medical Center,Chicago,60612,United States
6.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Shu，Bing,Zhao，Yongjian,Zhao，Shitian,et al. Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation[J]. Bone Research,2020,8(1).

Shu，Bing.,Zhao，Yongjian.,Zhao，Shitian.,Pan，Haobo.,Xie，Rong.,...&Chen，Di.(2020).Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation.Bone Research,8(1).

Shu，Bing,et al."Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation".Bone Research 8.1(2020).