Senescent cells exert a significant influence over their surrounding cellular environment. Senescent chondrocytes (SnChos) were found to be accumulated in degenerated cartilage present in joints affected by osteoarthritis. The influence of SnChos on exogenously transplanted stem cells has yet to be reported. In this study, we evaluated the interactions between SnChos and bone marrow mesenchymal stem cells (BMSCs) when co-cultured as well as in the intra-articular senescent microenvironment (IASM). The effect of IASM on cartilage regeneration was also assessed. It was found that a small fraction of SnChos induced BMSC cellular senescence and apoptosis. SnChos also inhibited proliferation, facilitated stemness, and suppressed chondrogenic differentiation of BMSCs. BMSCs induced the apoptosis of SnChos, reduced the proportion of SnChos, stimulated SnChos proliferation, and revealed a bidirectional effect on SnChos inflammaging. IASM significantly suppressed the survival, proliferation, and appropriate differentiation of grafted BMSCs in vivo, all of which impaired cartilage regeneration. Anti-senescence agent ABT-263 was able to partly rescue the cells from the negative effects of SnChos. The SnChos and BMSCs interacted with each other at cellular senescence, apoptosis, proliferation, differentiation, and cell functions. This interaction impaired the cartilage repair of MSCs. Anti-senescence agent provided a possible solution for this impairment.

Direct intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. However, the repair process was hindered by the absence of scaffold and poor cell–matrix interactions. In this study, we developed a pericellular collagen I coating (PCC) on MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation, and cartilage regeneration have been comprehensively evaluated in a New Zealand rabbit model. Firstly, we examined the morphology and physical characteristics of PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect homing were observed using multiscale methods. Thirdly, the precartilage condensation of cell pellets formed by aggregation of MSCs was examined to evaluate the cartilage-inducing potential of PCC. Finally, the cartilage regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically and histologically. In general, the cell adhesion and homing assay revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC homing and retention to cartilage defect. This increased homing ratio was accompanied by an increasing cell–cell contact. Compared with naked MSCs, the cell pellets formed by PCC-coated MSCs exhibited more evident appearance of condensation. In pellets, cell–cell interaction has been significantly stimulated, inducing the expression of condensation marker N-cadherin, and subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI, cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC significantly enhances the quality of cartilage regeneration judging from macroscopic observation, ICRS score, histological examination, and collagen type I, II, and X immunohistochemical staining. The capacity and viability of MSCs can be enhanced by collagen I coating, which provides cues for enhancing cell homing and differentiation. Our method provides a novel strategy for stem cell therapy.

Purpose: To conduct a solid evidence by synthesizing meta-analyses and updated RCTs about the effects of vitamin D on all-cause mortality in different health conditions.Methods: Data sources: Pubmed, Embase, Web of Science, the Cochrane Library, Google Scholar from inception until 25th April, 2022. Study selection: English-language, meta-analyses and updated RCTs assessing the relationships between vitamin D and all-cause mortality. Data synthesis: Information of study characteristics, mortality, supplementation were extracted, estimating with fixed-effects model. A Measurement Tool to Assess Systematic Reviews, Grading of Recommendations Assessment, Development and Evaluation, and funnel plot was used to assess risk of bias. Main outcomes: All-cause mortality, cancer mortality, cardiovascular disease mortality.Results: In total of 27 meta-analyses and 19 updated RCTs were selected, with a total of 116 RCTs and 149, 865 participants. Evidence confirms that vitamin D reduces respiratory cancer mortality (RR, 0.56 [95%CI, 0.33 to 0.96]). All-cause mortality is decreased in patients with COVID-19 (RR, 0.54[95%CI, 0.33 to 0.88]) and liver diseases (RR, 0.64 [95%CI, 0.50 to 0.81]), especially in liver cirrhosis (RR, 0.63 [95%CI, 0.50 to 0.81]). As for other health conditions, such as the general health, chronic kidney disease, critical illness, cardiovascular diseases, musculoskeletal diseases, sepsis, type 2 diabetes, no significant association was found between vitamin D and all-cause mortality.Conclusions: Vitamin D may reduce respiratory cancer mortality in respiratory cancer patients and all-cause mortality in COVID-19 and liver disorders' patients. No benefits showed in all-cause mortality after vitamin D intervention among other health conditions. The hypothesis of reduced mortality with vitamin D still requires exploration.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=252921, identifier: CRD42021252921.

Background: Bibliometrics is a methodology that measures the scientific output of an author, institution, or country. Visualized analysis is the transformation of data into visible form by software, highlighting important features, including commonalities and anomalies, allowing users to easily and quickly perceive significant aspects of their data. Purpose: To conduct a bibliometric analysis of the literature on anterior cruciate ligament (ACL) repair, with visualization of trends, in order to identify the areas of interest and the primary researchers involved in ACL repair. Study Design: Cross-sectional study. Methods: The PubMed database was queried on April 14, 2022, for publications that reported on ACL repair from 1960 onward. The initial search resulted in 1392 publications. Filter settings were applied to remove publications with weak correlation, such as those on meniscal repair and ACL reconstruction. Publication information, citations, authors, commonly used terms, and affiliated institutions and countries were analyzed by VOSviewer and Python. Results: A total of 553 articles were included for analysis. Three techniques were visualized: bridge-enhanced ACL repair, internal brace, and dynamic intraligamentary stabilization. The most published authors were Martha Murray (51 articles), Gregory Difelice (35 articles), and Braden Fleming (31 articles). The most cited article was “Collagen–Platelet Rich Plasma Hydrogel Enhances Primary Repair of the Porcine Anterior Cruciate Ligament” by Murray et al. The journals with the most publications on ACL repair were the American Journal of Sports Medicine (n = 49); Knee Surgery, Sports Traumatology, Arthroscopy (n = 49); and Arthroscopy (n = 48). The top 3 institutions by publication number were the Hospital for Special Surgery (n = 51), Boston Children’s Hospital (n = 49), and Brown University (n = 31), with the most publications coming from the United States (n = 242), Germany (n = 83), and the United Kingdom (n = 47). Conclusion: The results demonstrate that the research on ACL repair comes from a small number of authors and corresponding institutions; the top sports medicine journals and the developed countries have an interest in this topic.