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Calcif Tissue Int. 2019 Apr 25. doi: 10.1007/s00223-019-00552-x. [Epub ahead of print]

Ablation of Stabilin-1 Enhances Bone-Resorbing Activity in Osteoclasts In Vitro.

Author information

1
Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea.
2
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
3
Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju, Republic of Korea.
4
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
5
Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea.
6
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.
7
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.
8
Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea. kjeun@knu.ac.kr.
9
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. kjeun@knu.ac.kr.

Abstract

Stabilin-1 is a transmembrane receptor that regulates molecule recycling and cell homeostasis by controlling the intracellular trafficking and participates in cell-cell adhesion and transmigration. Stabilin-1 expression is observed in various organs, including bones; however, its function and regulatory mechanisms in the bone remain unclear. In this study, we evaluated the physiological function of stabilin-1 in bone cells and tissue using a stabilin-1 knockout (Stab1 KO) mouse model. In wild-type (WT) mice, stabilin-1 was expressed in osteoblasts and osteoclasts, and its expression was maintained during osteoblast differentiation but significantly decreased after osteoclast differentiation. There was no difference in osteoblast differentiation and function, or the expression of osteoblast differentiation markers between mesenchymal stem cells isolated from Stab1 KO and WT mice. However, osteoclast differentiation marker levels demonstrated a non-significant increase and bone-resorbing activity was significantly increased in vitro in RANKL-induced osteoclasts from Stab1-deficient bone marrow macrophages (BMMs) compared with those of WT BMMs. Microcomputed tomography showed a negligible difference between WT and Stab1 KO mice in bone volume and trabecular thickness and number. Moreover, no in vivo functional defect in bone formation by osteoblasts was observed in the Stab1 KO mice. The osteoclast surface and number showed an increased tendency in Stab1 KO mice compared to WT mice in vivo, but this difference was not statistically significant. Overall, these results indicate that Stab1 does not play an essential role in in vivo bone development and bone cell function, but it does affect in vitro osteoclast maturation and function for bone resorption.

KEYWORDS:

Bone marrow macrophages; Bone resorption; Deficiency; Osteoclast maturation; Stabilin-1 (Stab1)

PMID:
31025051
DOI:
10.1007/s00223-019-00552-x

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