Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes
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ORIGINAL RESEARCH
Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes Dong Ding1 · Xiao Yang1 · Hui‑qin Luan2 · Xin‑tong Wu1 · Cai He1 · Lian‑wen Sun1 · Yu‑bo Fan1,2 Received: 6 May 2020 / Accepted: 4 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Primary cilia are responsible for sensing mechanical loading in osteocytes. However, the underlying working mechanism of cilia remains elusive. An osteocyte model is necessary to reveal the role of cilia. Furthermore, the osteocyte model should be with upregulated or downregulated primary cilium expression. Herein, we used a pharmacological method to regulate the cilium formation of osteocytes. After screening, some pharmacological agents can regulate the cilium formation of osteocytes. We performed a CCK-8 assay to analyze the optimal working conditions of the drugs for MLO-Y4 cells. The agents include chloral hydrate (CH), Gd3+, Li+, and rapamycin. The expression of cilia affects the cellular functions, including mechanosensitivity, of osteocytes. Results showed that CH downregulated the cilium formation and ciliogenesis of osteocytes. In addition, Gd3+, Li+, and rapamycin upregulated the cilium expression of osteocytes. Moreover, the cilium expression positively correlated with the mechanosensitivity of osteocytes. This work reveals the role of primary cilia in the mechanosensing of osteocytes. Keywords Primary cilia · Osteocyte · Cilium formation · Mechanosensitivity · Bone
Introduction Bone disease, such as osteoporosis, hypogravity-induced osteopenia, and bone fractures, is associated with dysfunction of osteocytes. Osteocytes are mechanosensory cells in skeletal tissue [1] that respond to mechanical loading and regulate bone remodeling in adults [2]. The dysfunction of osteocytes is usually expressed as change in mechanosensitivity [3]. The reasons behind changes in osteocyte mechanosensitivity, however, are still unknown. Cellular sensors govern the mechanosensitivity of osteocytes. In order to
* Lian‑wen Sun [email protected] * Yu‑bo Fan [email protected] 1
Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing 100083, China
Beijing Key Laboratory of Rehabilitation Technical Aids for Old‑Age Disability, National Research Center for Rehabilitation Technical Aids, Beijing 100176, China
2
respond to loading, osteocytes interact with the interstitial fluid flow in the lacuna–canalicular system [4]. During this process, osteocytes activate multiple sensors that respond to external signals [5]. The major mechanosensors reported until now are the cytoskeleton, dendritic processes, integrin-based focal adhesions, connexin-based intercellular junctions, ion channels, extracellular matrix, and primary cilia [6]. Primary cilia stand out among a wide range o
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