Abstract
BackgroundDegenerative 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.MethodsTo 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.ResultsGene 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.ConclusionThe information obtained from bone cells and OLCS exosomes will help us discover new features of bone ageing.
Highlights
Degenerative changes in the skeleton play an important role in ageing
Mechanical stress is an effective stimulus for osteocytes to release messengers such as ATP, nitric oxide (NO), and prostaglandin E2 (PGE2) [4,5,6], which transport through the lacunar-canalicular system (LCS) and gap junctions between adjacent cells to the osteogenic surface to prompt osteoblast-mediated bone formation and directly inhibit osteoclast activation [7,8,9]
The morphological changes in aged bone Compared with young bones, aged bones displayed significant decreases in bone mass indicated by the reduced micro-CT parameters of bone volume to total volume ratio (BV/TV), Tb.N, and cortical bone thickness (CBT) (Fig. 1a–g)
Summary
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). 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. The endocrine function of the bone has gradually gained more attention, as bone-derived hormones and substances (OCN, FGF23, and LCN2) have been identified as regulating the homeostasis of metabolism, calcium phosphorus, and even innate immune responses and cognition [16,17,18,19,20]. Osteoimmunology studies have shown cross-regulatory mechanisms between bone and the immune system, especially in skeleton degenerative diseases such as osteoporosis and osteoarthritis. The above evidence prompts us to probe the correlation between bone secretion and ageing
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