Osteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole “organ” including cartilage, subchondral bone, synovium, and muscles. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the pathogenesis of age-related diseases including OA. In this review, we mainly focus on the role of the senescent skeletal cells (chondrocytes, osteoblasts, osteoclasts, osteocyte, and muscle cells) in initiating the development and progression of OA alone or through cross-talk with the macrophages/synovial cells. Accordingly, we summarize the current OA-targeted therapies based on the abovementioned theory, e.g., by eliminating senescent skeletal cells and/or inhibiting the senescence-associated secretory phenotype (SASP) that drives senescence. Furthermore, the existing animal models for the study of OA from the perspective of senescence are highlighted to fill the gap between basic research and clinical applications. Overall, in this review, we systematically assess the current understanding of cellular senescence in OA, which in turn might shed light on the stratified OA treatments.

Chondrosarcoma (CHS) is the second most common bone malignancy with limited therapeutic approaches. Our previous study has found that Yes associated protein 1 (YAP1) is downregulated in CHS cells treated with bromodomain and extraterminal domain (BET) inhibitor JQ1. However, the precise role of YAP1 in CHS is largely unknown. Herein, we found that YAP1 expression was upregulated in CHS tissues, and positively correlated with its grading score. Loss of YAP1 inhibited CHS proliferation and induced cellular senescence, while expression of YAP1 mutants revealed YAP1/TEA domain family member (TEAD)-dependent negative regulation of p21 and subsequent cellular senescence. These results were validated by in vivo experiments using stable shYAP1 cell lines. Mechanistically, negative regulation of p21 by YAP1 occurred post-transcriptionally via Dicer-regulated miRNA networks, specifically, the miR-17 family. Furthermore, we demonstrated that sequential targeting of YAP1 and p21 enhanced the elimination of JQ1-induced senescent cells in a Bcl-2-like 1 (Bcl-XL)/Caspase-3 dependent manner. Altogether, we unveil a novel role of YAP1 signaling in mediating CHS cell senescence and propose a one-two punch approach that sequentially targets the YAP1/p21 axis to eliminate senescent cells.

Dendritic cells (DCs)-based tumor vaccines have the advantages of high safety and rapid activation of T cells, and have been approved for clinical tumor treatment.However, the conventional DC vaccines have some severe problems, such as poor activation of DCs in vitro, low level of antigen presentation, reduced cell viability, and difficulty in targeting lymph nodes in vivo, resulting in poor clinical therapeutic effects. In this research, magnetic nanoparticles Fe 3 O 4 @Ca/MnCO 3 were prepared and used to actively and efficiently deliver antigens to the cytoplasm of DCs, promote antigen cross-presentation and DC activation, and finally enhance the cellular immune response of DC vaccines. The results show that the magnetic nanoparticles can actively and quickly deliver antigens to the cytoplasm of DCs by regulating the magnetic field, and achieve cross-presentation of antigens. At the same time, the nanoparticles degradation product Mn 2+ enhanced immune stimulation through the interferon gene stimulating protein (STING) pathway, and another degradation product Ca 2+ ultimately promoted cellular immune response by increasing autophagy.The DC vaccine constructed with the magnetic nanoparticles can more effectively migrate to the lymph nodes, promote the proliferation of CD8 + T cells, prolong the time of immune memory, and produce higher antibody levels. Compared with traditional DC vaccines, cytoplasmic antigen delivery with the magnetic nanoparticles provides a new idea for the construction of novel DC vaccines.

Computer‐assisted orthopedic system (CAOS) is rapidly gaining popularity in the field of precision medicine. However, the cost‐effectiveness of CAOS has not been well clarified. We performed this review to summarize and assess the cost‐effectiveness analyses (CEAs) with regard to CAOS. Publications on CEA in CAOS have been searched in PubMed and CEA Registry up to May 31, 2022. The Quality of Health Economic Studies (QHES) instrument was used to estimate the quality of studies. Relationships between qualities and potential factors were also examined. There were 15 eligible studies in the present review. Twelve studies evaluated CAOS joint arthroplasties and found that CAOS joint arthroplasties were cost‐effective compared to manual methods. Three studies focused on spinal surgery, two of which analyzed the cost‐effectiveness of CAOS for patients after spinal fusion, with conflicting results. One study demonstrated that CAOS was cost‐effective in spinal pedicle screw insertion. The mean QHES score of CEAs included was 86.1. The potential factors had no significant relationship with the quality of studies. Based on available studies, our review reflected that CAOS was cost‐effective in the field of joint arthroplasty. While in spinal surgery, the answer was unclear. Current CEAs represent high qualities, and more CEAs are required in the different disciplines of orthopedics where CAOS is employed.