Preliminary study of short-term outcomes and learning curves of robotic-assisted THA: comparison between closed platform robotic system and open platform robotic system.

BACKGROUND: Both closed platform and open platform robotic-assisted total hip arthroplasty (THA) have recently been recommended as a viable treatment option for achieving accurate positioning of components. Yet, limited studies paid attention to the differences between the closed platform robotic system and the open platform robotic system. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and learning curve of two systems. MATERIALS AND METHODS: We retrospectively included 62 patients (31 closed robotic system and 31 open robotic system) who underwent THA between February 2021 and January 2023. The demographics, operating time, cup positioning, complications and hip Harris score were evaluated. Learning curves of operation time was conducted using cumulative sum (CUSUM) analysis. RESULTS: There were no differences in surgical time (76.7 ± 12.1 min vs. 72.3 ± 14.8 min), estimated blood loss (223.2 ± 13.2 ml vs. 216.9 ± 17 ml) and Harris Hip score (HHS) between closed platform robotic system and the open platform robotic system. The closed robotic system and the open robotic system were associated with a learning curve of 9 cases and 7 cases for surgical time respectively, based on the satisfying rate of Lewinnek's safe zone outliers (1/31, 96.8%) and no occurrence of complication. Both robotic systems had significant reduction in overall surgical time, the duration of acetabulum registration, and estimated blood loss between learning phase and proficiency phase. CONCLUSION: The authors suggest that the surgical outcomes and safe zone outlier rate of the open robotic-assisted THA were similar to those of the closed robotic-assisted THA. These two robotic-assisted are associated with comparable learning curves and both have the precise positioning of acetabular component. From learning phase to proficiency phase, the rate of positions within the safe zone differed only marginally (88.9-100% vs. 85.7-100%) based on a rather low number of patients. This is not a statistically significant difference. Therefore, we suggest that THA undergoing with the robotic-assisted system is the relatively useful way to achieve planned acetabular cup position so far.

Single-Cell RNA Sequencing Reveals Transcriptional Changes in the Cartilage of Subchondral Insufficiency Fracture of the Knee.

Purpose: Subchondral insufficiency fracture of the knee (SIFK) is a common cause of knee joint pain that mainly afflicts the elderly. Until now, how a sudden insufficiency fracture of subchondral bone affects the transcriptomic profiles of cartilage in SIFK and OA patients are largely unknown. Methods: Single-cell RNA sequencing (scRNA-seq) was used to identify various cell subsets and evaluate transcriptomic differences in cartilage of SIFK and OA patients. In addition, the above findings were confirmed by histological evaluation and immunohistochemical (IHC) staining. Results: We found that the transcriptomic profiles of cartilage in the SIFK patient was completely different from those of normal and OA patients. Accordingly, several novel cell clusters with activation of hypoxia and endochondral ossification signaling were identified in the SIFK cartilage. Chondrocyte trajectories analysis and IHC staining revealed that transcription factors including TCF4 were found to be highly up-regulated during the occurrence of SIFK, which might drive the reactive formation of cartilage and fibrous tissue and the activation of endochondral ossification. Conclusion: This is the first report to elucidate the transcriptomic alterations and distinct cell type subpopulations in the cartilage of SIFK and OA by the use of scRNA-seq, which provides a new insight in the understanding of the initiation and progression of SIFK.

Senescent skeletal cells cross-talk with synovial cells plays a key role in the pathogenesis of osteoarthritis.

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.

Sequential targeting of YAP1 and p21 enhances the elimination of senescent cells induced by the BET inhibitor JQ1.

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.