Mechanical force induces macrophage-derived exosomal UCHL3 promoting bone marrow mesenchymal stem cell osteogenesis by targeting SMAD1.

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.

Schwann Cell-derived exosomes promote bone regeneration and repair by enhancing the biological activity of porous Ti6Al4V scaffolds.

Implants made of porous titanium alloy and fabricated by 3D printing are increasingly used in clinical research. However, porous titanium alloys do not integrate very well with surrounding bone tissue, and bone ingrowth into the implants is not substantial. Schwann cells (SCs) and SC-derived exosomes can effectively promote nerve regeneration, but their role in bone tissue regeneration and repair has not been studied. Therefore, we added SC-derived exosomes to bone marrow stromal cell (BMSC) cultures and observed their effect on BMSCs in vitro; then, we combined exosomes with porous Ti6Al4V scaffolds and observed their effects on bone regeneration and repair in vivo. We found that SC-derived exosomes could promote the migration, proliferation and differentiation of BMSCs and that combining exosomes with porous titanium alloy can effectively improve the efficacy of titanium alloy scaffolds in bone repair. The combination of exosomes and porous Ti6Al4V implants may constitute a new therapeutic strategy for treating bone defects.

Frequency-related viscoelastic properties of the human incisor periodontal ligament under dynamic compressive loading.

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 tanδ 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.