Exosomes derived from M2 macrophages induce angiogenesis to promote wound healing.

There is an urgent clinical need for an appropriate method to shorten skin healing time. Among most factors related to wound healing, M2 macrophages will be recruited to the wound area and play a pivotal role in a time-limiting factor, angiogenesis. The exploration of exosomes derived from M2 in angiogenesis promotion is an attractive research field. In this project, we found that exosomes from M2 (M2-EXO) promoted the angiogenic ability of HUVECs in vitro. With a series of characteristic experiments, we demonstrated that M2-EXO inhibited PTEN expression in HUVECs by transferring miR-21, and further activated AKT/mTOR pathway. Then, using a full-thickness cutaneous wound mice model, we demonstrated that M2-EXO could be used as a promotor of angiogenesis and regeneration in vivo. Furthermore, M2-EXO-treated skin wounds exhibited regeneration of functional microstructures. These results demonstrate that M2-EXO can be used as a promising nanomedicine strategy for therapeutic exploration of skin healing with the potential to be translated into clinical practice.

Causal Relationships of General and Abdominal Adiposity on Osteoarthritis: A Two-Sample Mendelian Randomization Study.

Background: Adiposity is closely related to osteoarthritis, but the causal effects of different types of adiposity on osteoarthritis are indistinct. This study conducted a Mendelian Randomization (MR) analysis for the causal effects of general adiposity and abdominal adiposity on knee osteoarthritis (KOA) and hip osteoarthritis (HOA). Methods: The general adiposity was assessed by body mass index (BMI), while the abdominal adiposity was evaluated with waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). The data used in this two-sample MR analysis originated from genome-wide association studies (GWAS). Significant (p < 5 × 10−8) and independent (r2 < 0.01) single-nucleotide polymorphisms were selected as instrumental variables for the MR analysis. Subsequently, this study used the inverse variance weighted, weighted median, and other methods for the causal inference, and the results were presented as odds ratios (OR). Moreover, sensitivity analyses were conducted to assess the stability and reliability of the results. Results: The MR results revealed positive causal effects of BMI on KOA (OR: 1.694; 95% CI: from 1.492 to 1.923; p = 3.96 × 10−16) and HOA (OR: 1.412; 95% CI: from 1.196 to 1.666; p = 4.58 × 10−5). Additionally, WC and HC both positively and causally related to KOA (WC: OR: 1.827; 95% CI: from 1.564 to 2.134; p = 2.68 × 10−14; HC: OR: 1.610; 95% CI: from 1.357 to 1.912; p = 5.03 × 10−8) and HOA (WC: OR: 1.491; 95% CI: from 1.254 to 1.772; p = 5.85 × 10−6; HC: OR: 1.439; 95% CI: from 1.205 to 1.719; p = 5.82 × 10−5). However, no causal relationship existed between WHR and obesity. These results were robust according to the sensitivity analyses. Conclusions: This study indicated that both general and abdominal obesity had positive causal effects on knee osteoarthritis and hip osteoarthritis.