Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function / 国际口腔科学杂志·英文版

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.

[Clinical experience of penile elongation: a comparison of four different operative approaches].

OBJECTIVE: To investigate the curative effect of penile elongation with four differentoperative approaches. METHODS: Through four different operative approaches (the coronary sulcus ringincision, Y or Z shaped incision or Z shaped incision combined with coronary sulcus ring incision), thepenile skin and fascia were degloved until the penile root. Then the superficial and deep dorsal penilesuspensory ligament were cut off. After electric coagulation of the residue ends, the two-side tissue at thefront of the pubic symphysis was sutured. Then the penile skin and fascia were repositioned and the incisionat the inner and outer plate was closed. RESULTS: The increased penile static length was (2.9 ± 0.2) cmwith abdominal wall Y incision (12 cases); (3.1 ± 0.3) cm with transabdominal modified Z incision (260 cases); (3.9 ± 0.7) cm with coronary sulcus ring incision (363 cases); (3.4 ± 0.8) cm with combined incision (39 cases). The lengthening effect was significantly different between the coronary ring incision and abdominal wall Y/Z incision (P < 0.05). The postoperative follow-up period was 6 months to 5.5 years without serious complications. Only 3 cases of subcutaneous hematoma occurred with treatment of debridement and drainage. 4 cases with ischemic necrosis at distal penile skin, were treated with debridement, dressing and physiotherapy, leaving no scar. CONCLUSIONS: Penile lengthening surgery are safe and effective through different approaches. The coronal ring incision has the best therapeutic effect.