Ageing characteristics of bone indicated by transcriptomic and exosomal proteomic analysis of cortical bone cells

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(2019) 14:129

RESEARCH ARTICLE

Open Access

Ageing characteristics of bone indicated by transcriptomic and exosomal proteomic analysis of cortical bone cells Chenyang Zhang1, Shuyu Xu1, Shufan Zhang1, Mengmeng Liu1, Haiming Du1, Ruinan Sun1, Bo Jing2 and Yao Sun1*

Abstract Background: Degenerative changes in the skeleton play an important role in ageing. As the foremost sensors and orchestrators of bone remodelling, osteocytes contribute significantly to the health of the skeleton. Embedded in a mineralized bone matrix, the osteocyte network and the surrounding lacunar canaliculae work together as a functional syncytium—the osteocytic lacunar-canalicular system (OLCS). However, changes in the OLCS during ageing and related mechanisms cannot be fully understood by using traditional histological analysis. Methods: To link the phenotypes of aged osteocytes and their functional changes during ageing, we analysed the changes in the gene expression profiles of bone cells and the proteomic profiles of OLCS exosomes derived from aged and young cortical bone. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) suggested that a decline in cell energy metabolism and an increased level of the proinflammatory state are major characteristics of bone ageing. Moreover, some DEGs were key regulators of bone mechanical sensation and bone remodelling, which are indicative of reduced bone-specific function with age. Further, the identified proteins in OLCS exosomes showed potential changes in the secretory function bone. Compared with young controls, the decreased functional proteins in aged OLCS exosomes were enriched mainly in GO terms that included regulating bone development and remodelling, cell-matrix adhesion, and cell clearance and homeostasis. Notably, several functions of exosomal proteins of the aged group revealed potential new roles, such as regulating innate and adaptive immunity, wound healing, and angiogenesis and eliminating oxidative stress. Conclusion: The information obtained from bone cells and OLCS exosomes will help us discover new features of bone ageing. Keywords: Bone ageing, Gene expression profiling, Exosome, OLCS

Background Osteocytes, the most numerous cell populations in bone, are responsible for sensing mechanical force and acting as the “hub” of the regulatory network for bone remodelling. The osteocyte network and the lacunar canaliculae constitute a functional syncytium—the osteocytic * Correspondence: [email protected] 1 Department of Oral Implantology, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Middle Yanchang Road, Shanghai 200072, China Full list of author information is available at the end of the article

lacunar-canalicular system (OLCS) [1–3], underscoring that the function of osteocytes cannot be implemented without cell-to-cell connections and their 3D physiological environment. Mechanical stress is an effective stimu