Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells(MSCs)are essential for periodontal regeneration.However,the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs.Apoptotic bodies(ABs)are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment,thus we investigated the effects of ABs derived from MSCs on periodontitis.MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h,after which ABs were isolated from the culture supernatant using a multi-filtration system.The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption.miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects.Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p,which interferes with the function of osteoclasts.Additionally,DC-STAMP is a key regulator that mediates membrane infusion.ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes,which mediates the engulfment of ABs by pre-osteoclasts.ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts.Collectively,MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP,which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts,which in turn led to the attenuation of their differentiation and bone resorption.These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

Purpurolide C-based microneedle promotes macrophage-mediated diabetic wound healing via inhibiting TLR4-MD2 dimerization and MYD88 phosphorylation

Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum,was found to promote diabetic wound healing.To investigate the key regulation targets of PC,in vitro RNA-seq,molecular docking calcula-tions,TLR4-MD2 dimerization SDS-PAGE detection,and surface plasmon resonance(SPR)were per-formed,indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation.Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing.Furthermore,a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC(PC@MLIP MN)was developed,which overcame the poor water solubility and weak skin permeability of PC,so that successfully punctured the skin and delivered PC to local tissues,and accurately regulated macrophage polarization in diabetic wound management.Overall,PC is an anti-inflammatory small molecule compound with a well-defined structure and dualtarget regulation,and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

OsSIDP366,a DUF1644 gene,positively regulates responses to drought and salt stresses in rice

Domain of unknown function 1644 （DUF1644） is a highly conserved amino acid sequence motif present only in plants. Analysis of expression data of the family of DUF1644- containing genes indicated that they may regulate responses to abiotic stress in rice. Here we present our discovery of the role of Os.SIDP366, a member of the DUF1644 gene family, in response to drought and salinity stresses in rice. Transgenic rice plants overexpressing OsSIDP366 showed enhanced drought and salinity tolerance and reduced water loss as compared to that in the control, whereas plants with downregulated OsSIDP366 expression levels using RNA interference （RNAi） were more sensitive to salinity and drought treatments. The sensitivity to abscisic acid （ABA） treatment was not changed in OsStDP366-overexpressing plants, and OsSIDP366 expression was not affected in ABA- deficient mutants. Subcellular localization analysis revealed that OsSIDP366 is presented in the cytoplasmic foci that colocalized with protein markers for both processing bodies （PBs） and stress granules （SGs） in rice protoplasts. Digital gene expression （DGE） profile analysis indicated that stress-related genes such as SNACl, OsHAK5 and PRs were upregulated in OsSIDP366-overexpressing plants. These results suggest that OsSIDP366 may function as a regulator of the PBs/SGs and positively regulate salt and drought resistance in rice.