A Regulatory Role of ANTXR1 in RANKL-Induced Osteoclast Differentiation and Function

Myeung Su Lee¹, Changhoon Lee², Chong Hyuk Chung³, Wan-Hee Yoo⁴, Jin Jung Choi⁵, Jong Min Baek⁶ and Ju-Young Kim⁷, ¹Department of Rheumatology, Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, Iksan, Korea, Republic of (South), ²Division of Rheumatology, Department of Internal Medicine, Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, Iksan, Korea, Republic of (South), ³Division of Rheumatology, Department of Internal Medicine, Wonkwnag University Hospital, Division of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital, IKSAN, Korea, Republic of (South), ⁴Division of Rheumatology, Department of Internal Medicine, Research Institute of Clinical Medicine of chonbuk national university-Biomedical Research Institute of chonbuk national university hospital, Jeonju, Korea, Republic of (South), ⁵Rheumatology, CHA University Medical Center at Bundang, Sungnam, Korea, Republic of (South), ⁶Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Korea, Republic of (South), ⁷Imaging Science-based Lung and Bone Diseases Research Center, School of Medicine, Wonkwang University, IKSAN, Korea, Republic of (South)

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Angiogenesis, Bone, osteoclasts and osteoporosis

Session Information

Date: Tuesday, October 23, 2018

Session Title: Osteoarthritis and Joint Biology – Basic Science Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Anthrax toxin receptor 1 (ANTXR1) has been known to have relationship with extracellular transmembrane protein deeply associated with the process of bone formation and exert important role in angiogenesis. However, there have been no reports to prove the effects of ANTXR1 on bone metabolism mediated by two types of bone cells, osteoclasts and osteoblasts. The aim of this study is to reveal the role of ANTXR1 in the differentiation and function of osteoclasts and osteoblasts.

Methods:

To determine the effect of ANTXR1 on osteoclastogenesis or osteoblast differentiation, we examined TRAP staining, F-actin staining and Pit assay, or ALP and Alizarin Red-mineralization staining, respectively. The mechanism of ANTXR1 by transfection of retrovirus or siRNA analyzed using real-time PCR and western blot analysis. Also, the effect of ANTXR1 on osteoclast-mediated angiogenesis of endothelial cells assessed by in vitro vascular tubule formation assay of human umbilical vein endothelial cells (HUVECs).

Results:

Through performing gain- and loss-of-function studies, we found that ANTXR1 positively regulated receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation and bone resorption with no effects on osteoblast differentiation. During ANTXR1-mediated regulation of osteoclastogenesis, phosphorylation of early signal transducers, c-jun N-terminal kinase (JNK), Akt, and inhibitor of kappa B (IB) was affected, which in turn alteration of mRNA and protein levels of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In addition, genetic manipulation of ANTXR1 in bone marrow macrophages (BMMs) modulated the capillary-like tube formation by HUVECs via two kinds of angiogenic factors, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-A (VEGF-A). These results explained the important role of ANTXR1 in osteoclast differentiation and functional activity, as well as, osteoclast-mediated angiogenesis of endothelial cells.

Conclusion:

Taken together, it was proposed that ANTXR1 might be a promising candidate for gene therapy related with bone metabolic diseases and further, have potential to be served as an important biomarker in the research fields of bone metastasis associated with vascularization.

Disclosure: M. S. Lee, None; C. Lee, None; C. H. Chung, None; W. H. Yoo, None; J. J. Choi, None; J. M. Baek, None; J. Y. Kim, None.

To cite this abstract in AMA style:

Lee MS, Lee C, Chung CH, Yoo WH, Choi JJ, Baek JM, Kim JY. A Regulatory Role of ANTXR1 in RANKL-Induced Osteoclast Differentiation and Function [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/a-regulatory-role-of-antxr1-in-rankl-induced-osteoclast-differentiation-and-function/. Accessed April 8, 2020.

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