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Studies concerning the mechanical properties of the human periodontal ligament under dynamic compression are rare. This study aimed to determine the viscoelastic properties of the human periodontal ligament under dynamic compressive loading. Ten human incisor specimens containing 5 maxillary central incisors and 5 maxillary lateral incisors were used in a dynamic mechanical analysis. Frequency sweep tests were performed under the selected frequencies between 0.05 Hz and 5 Hz with a compression amplitude that was 2% of the PDL’s initial width. The compressive strain varied over a range of 4%-8% of the PDL’s initial width. The storage modulus, ranging from 28.61 MPa to 250.21 MPa, increased with the increase in frequency. The loss modulus (from 6.00 MPa to 49.28 MPa) also increased with frequency from 0.05 Hz– 0.5 Hz but remained constant when the frequency was higher than 0.5 Hz. The tan δ showed a negative logarithmic correlation with frequency. The dynamic moduli and the loss tangent of the central incisor were higher than those of the lateral incisor. This study concluded that the human PDL exhibits viscoelastic behavior under compressive loadings within the range of the used frequency, 0.05 Hz– 5 Hz. The tooth position and testing frequency may have effects on the viscoelastic properties of PDL.

Background Orthodontic tooth movement (OTM), a process of alveolar bone remodelling, is induced by mechanical force and regulated by local inflammation. Bone marrow-derived mesenchymal stem cells (BMSCs) play a fundamental role in osteogenesis during OTM. Macrophages are mechanosensitive cells that can regulate local inflammatory microenvironment and promote BMSCs osteogenesis by secreting diverse mediators. However, whether and how mechanical force regulates osteogenesis during OTM via macrophage-derived exosomes remains elusive. Results Mechanical stimulation (MS) promoted bone marrow-derived macrophage (BMDM)-mediated BMSCs osteogenesis. Importantly, when exosomes from mechanically stimulated BMDMs (MS-BMDM-EXOs) were blocked, the pro-osteogenic effect was suppressed. Additionally, compared with exosomes derived from BMDMs (BMDM-EXOs), MS-BMDM-EXOs exhibited a stronger ability to enhance BMSCs osteogenesis. At in vivo, mechanical force-induced alveolar bone formation was impaired during OTM when exosomes were blocked, and MS-BMDM-EXOs were more effective in promoting alveolar bone formation than BMDM-EXOs. Further proteomic analysis revealed that ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3) was enriched in MS-BMDM-EXOs compared with BMDM-EXOs. We went on to show that BMSCs osteogenesis and mechanical force-induced bone formation were impaired when UCHL3 was inhibited. Furthermore, mothers against decapentaplegic homologue 1 (SMAD1) was identified as the target protein of UCHL3. At the mechanistic level, we showed that SMAD1 interacted with UCHL3 in BMSCs and was downregulated when UCHL3 was suppressed. Consistently, overexpression of SMAD1 rescued the adverse effect of inhibiting UCHL3 on BMSCs osteogenesis. Conclusions This study suggests that mechanical force-induced macrophage-derived exosomal UCHL3 promotes BMSCs osteogenesis by targeting SMAD1, thereby promoting alveolar bone formation during OTM. Graphical Abstract