Healthy periodontal tissues are the basis for maintaining tooth stability and masticatory function. During masticatory movements, teeth are continuously subjected to various mechanical stimuli (Fan & Caton, 2018). As a particular force-sensing tissue in the stomatognathic system, the periodontal ligament is closely related to mechanical stimuli (Thompson et al., 2012, van Oers et al., 2015). It senses the strength, location and direction of mechanical stimuli on the teeth and disperses and transmits the stimuli to the surrounding tissues, thus inducing remodeling of the periodontal tissues (Hao et al., 2009, Pavasant and Yongchaitrakul, 2011).

PDLCs and osteoblasts play essential roles in the remodeling process associated with the mechanical stimulation of periodontal tissues. First, studies have shown that PDLCs sense mechanical signals and convert them into biological signals to regulate periodontal bone remodeling (Xu et al., 2012, Zhong et al., 2008). Meanwhile, osteoblasts are the central bone-forming cells that produce many proteins required for bone formation, such as alkaline phosphatase (Alp), osteocalcin (OCN), and collagen type I (Col-1) (Long, 2011, Saint-Pastou Terrier and Gasque, 2017). However, when PDLCs sense mechanical signals, the pathway through which they are transmitted to osteoblasts and ultimately participate in tissue remodeling remains unclear.

Recently, exosome-mediated intercellular communication has drawn increasing attention. Theoretically, exosomes can be secreted by a whole range of cells and are widely distributed in body fluids (Camussi et al., 2010). Exosomes have been shown to carry proteins, lipids and nucleic acids secreted by cells and function in various physiological and pathological processes in autocrine and paracrine manners (Chevillet et al., 2014). It has been established that exosomes play an important role in periodontal tissue remodeling. Zhao et al. (Zhao et al., 2019) found that LPS could promote the secretion of exosomes by PDLCs, and these exosomes would inhibit the osteogenic activity of osteoblasts, which ultimately led to the destruction of periodontal bone, and the exosomes of PDLCs were likely to be the key to the destruction of periodontal tissues caused by periodontitis. Lv et al. (Lv et al., 2020) found that stretch loading could induce osteocytes to secrete exosomes and promote osteogenic differentiation of periodontal ligament stem cells (PDLSCs) by upregulating the expression of bone morphogenetic protein 2 (Bmp2) and runt-related transcription factor 2 (Runx2) in PDLSCs. Wang et al. ( Wang et al., 2021) found that osteoclast-derived exosomes showed the ability to inhibit PDLSCs' osteogenic differentiation under compression stress stimulation. All the above studies reflect that signaling between exosomes and bone cells plays an important role in periodontal tissue remodeling, but the molecular mechanism remains unclear.

Among the cargos carried by exosomes, miRNAs play a key role in signal transduction (Wang et al., 2020). Our previous study also showed that PDLC exosomes under cyclic stretch stimulation mediate communication between PDLCs and macrophages via miRNAs and participate in periodontal tissue remodeling (Wu et al., 2023). Therefore, we hypothesize that exosomes may also mediate mechanical signal transduction between PDLCs and osteoblasts. As small biological molecules with significant research potential, exosomes may reveal signaling pathways and mechanisms from a nanoscale perspective. In summary, the present study investigated the effects of exosomes secreted by PDLCs under mechanical stimulation on osteoblast differentiation and the downstream pathways, aiming to reveal the mechanisms of periodontal tissue remodeling induced by mechanical stimulation.