Cellular and Molecular Life Sciences

, Volume 76, Issue 2, pp 355–367 | Cite as

Chemokine-like receptor 1 deficiency leads to lower bone mass in male mice

  • Huashan Zhao
  • Dewen Yan
  • Liang Xiang
  • Chen Huang
  • Jian Li
  • Xiangfang Yu
  • Binbin Huang
  • Baobei Wang
  • Jie Chen
  • Tianxia Xiao
  • Pei-Gen RenEmail author
  • Jian V. ZhangEmail author
Original Article


The adipokine Chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), are associated with osteoblastogenic differentiation of mesenchymal stem cells (MSCs) and osteoclastogenic differentiation of osteoclast precursors in vitro, suggesting that CMKLR1 would affect the bone mineral density (BMD). However, the role of CMKLR1 on BMD in vivo remains unknown. Here, using CMKLR1 knockout mouse model, we unveiled that CMKLR1 effected the amount of Leydig cells in testis and regulated androgen-dependent bone maintenance in male mice, which exhibited lower serum testosterone levels, thereby reducing the trabecular bone mass. Correspondingly, the mRNA expression of testosterone synthesis enzymes in testis decreased. The bone tissue also showed decreased mRNAs expression of osteogenic markers and increased mRNA levels for osteoclast markers. Furthermore, by in vitro differentiation models, we found CMKLR1-deficiency could break the balance between osteoblastogenesis and osteoclastogenesis that caused a shift from osteogenic to adipogenic differentiation in MSCs and enhanced osteoclast formation. In addition, bone mass increase in CMKLR1 KO male mice can be promoted by treatment with 5α-dihydrotestosterone (DHT), and the inactivation of CMKLR1 in male wild-type (WT) mice with antagonist treatment can lead to low bone mass. Taken together, these data indicate that CMKLR1 positively regulates bone metabolism through mediating testosterone production and the balance between osteoblast and osteoclast formation.


Osteoporosis Chemerin CMKLR1 Adipokine Testosterone 



This study was supported by the National Natural Science Foundation of China (81771611 and 31671562), Guangdong Natural Science Foundation (2017A020211033), the Science and Technology Innovation Fund of Shenzhen (JCYJ20170413165233512, JCYJ20170412140326739, JCYJ20170413165503382, JCYJ20170815123502541, JCYJ20170814175916411, and JCYJ20170307165601938).

Author contributions

JZ, LX, HZ and PR conceived and designed the experiments; LX, HZ, BW, CH, XT, JL, XY and BH performed the experiments; LX, HZ, JZ DY, XY and BH analyzed the data; JC, DY and XT contributed reagents/materials/analysis tools/housing animals; HZ and LX wrote the manuscript. All authors reviewed and approved the final version of the manuscript.

Supplementary material

18_2018_2944_MOESM1_ESM.doc (3.1 mb)
Supplementary material 1 (DOC 3125 kb)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Huashan Zhao
    • 1
  • Dewen Yan
    • 2
  • Liang Xiang
    • 1
  • Chen Huang
    • 1
  • Jian Li
    • 3
  • Xiangfang Yu
    • 3
  • Binbin Huang
    • 1
    • 4
  • Baobei Wang
    • 1
  • Jie Chen
    • 1
  • Tianxia Xiao
    • 1
  • Pei-Gen Ren
    • 2
    Email author
  • Jian V. Zhang
    • 1
    Email author
  1. 1.Laboratory for Reproductive Health, Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina
  2. 2.Department of EndocrinologyThe First Affiliated Hospital of Shenzhen UniversityShenzhenChina
  3. 3.Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina
  4. 4.Shenzhen College of Advanced TechnologyUniversity of Chinese Academy of SciencesShenzhenChina

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