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

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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.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2016R1A2B4010043) and a Grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Korea (HI13C1874).

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Authors and Affiliations

  1. Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea

    Soon-Young Kim, Eun-Hye Lee & Jung-Eun Kim

  2. BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea

    Soon-Young Kim, Eun-Hye Lee & Jung-Eun Kim

  3. Department of Biochemistry, School of Medicine, Dongguk University, Gyeongju, Republic of Korea

    Seung-Yoon Park

  4. Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea

    Hyuck Choi & Jeong-Tae Koh

  5. Department of Oral Pathology and Regenerative Medicine, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea

    Eui Kyun Park

  6. Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea

    In-San Kim

  7. KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea

    In-San Kim

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Contributions

SYK and JEK contributed to the conception and design of the research. SYK, EHL, HC, and JTK performed the experiments and analyzed the data. SYP, EKP, ISK, and JEK interpreted the results of the experiments. SYK and JEK prepared the figures, and drafted and edited the manuscript. All authors approved the manuscript.

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Correspondence to Jung-Eun Kim.

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Conflict of interest

Soon-Young Kim, Eun-Hye Lee, Seung-Yoon Park, Hyuck Choi, Jeong-Tae Koh, Eui Kyun Park, In-San Kim, and Jung-Eun Kim declare no conflicts of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving animals were approved by the Institutional Animal Care and Use Committee and in accordance with the ethical standards of the institution at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Kim, SY., Lee, EH., Park, SY. et al. Ablation of Stabilin-1 Enhances Bone-Resorbing Activity in Osteoclasts In Vitro. Calcif Tissue Int 105, 205–214 (2019). https://doi.org/10.1007/s00223-019-00552-x

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