No abstract

Osteosarcoma is the most common malignant bone tumor in adolescents, and metastasis is the key reason for treatment failure and poor prognosis. Once metastasis occurs, the 5-year survival rate is only approximately 20%, and assessing and predicting the risk of osteosarcoma metastasis are still difficult tasks. In this study, cellular communication between tumor cells and nontumor cells was identified through comprehensive analysis of osteosarcoma single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, illustrating the complex regulatory network in the osteosarcoma microenvironment. In line with the heterogeneity of osteosarcoma, we found subpopulations of osteosarcoma cells that highly expressed COL6A1, COL6A3 and MIF and were closely associated with lung metastasis. Then, BCDEG, a reliable risk regression model that could accurately assess the metastasis risk and prognosis of patients, was established, providing a new strategy for the diagnosis and treatment of osteosarcoma.

Background: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing. Methods: A total of 88 rats were used in this study. Eight rats were killed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the TLF augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3 Â 5 mm defect of the supraspinatus was created. The TLF was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8, and 16 weeks postoperatively. Results: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 AE 0.71 vs. 24.40 AE 0.89, P ¼ .025) and 16 weeks (24.60 AE 0.55 vs. 26.40 AE 0.55, P .001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8, and 16 weeks (24.78% AE 2.76% vs. 20.67% AE 2.11% at 4 weeks, P ¼ .046; 25.46% AE 1.77% vs. 21.49% AE 2.33% at 8 weeks, P ¼ .026; 34.77% AE 2.25% vs. 30.01% AE 3.17% at 16 weeks, P ¼ .040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 AE 2.49 N vs. 23.10 AE 3.47 N, P ¼ .022). Conclusions: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for superior capsule reconstruction (SCR).

Background Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair and regeneration. Previously we found more adipocytes accumulated in the patellar tendon injury sites in aging rats compared with the young ones, of which the mechanism is still unknown. Here, we want to identify whether erroneous differentiation of TSPCs by aging accounts for the adipocyte accumulation. Methods TSPCs from young and aging rats were isolated and propagated. Both young and aging TSPCs were induced to differentiate into adipocytes, and Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunofluorescent staining were used to evaluate the capability of TSPCs. RNA sequencing was utilized to screen out different genes and signaling pathways related to adipogenesis between young and aging TSPCs. Results The Oil red O staining showed there were more adipocytes formed in young TSPCs. Besides, adipogenic markers perilipin, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins alpha (C/EBPα) and Fatty acid-binding protein 4 (FABP4) were elevated both at gene and protein level. PPARγ signaling pathway was selected as our target via RNA sequencing. After adding the signaling activators, Rosiglitazone maleate (RM), inhibited adipogenesis of aging TSCs was reversed. Conclusions In conclusion, aging inhibited adipogenesis of TSPCs by down‐regulating PPARγ signaling. It is not likely that the adipocyte accumulation in aging tendon during repair was due to the aging of TSPCs. This may provide new targets for curing aging tendon injuries or tendinopathies.