Previous studies identified that chondrocyte apoptosis serves an important role in osteoarthritis (OA). However, the mechanisms of cartilage degeneration induced by apoptosis remain unclear. The present study investigated the role of mitochondrial dysfunction in OA pathology. A total of 30 cartilage samples presenting an Outerbridge score ranging between 0 and III were collected during total knee arthroplasty. Half of the samples were embedded for observation by transmission electron microscopy. The remaining samples were digested, and chondrocytes were isolated from normal and OA tissues. Subsequently, the enzymatic activity of factors of the mitochondrial respiratory chain (MRC), and mitochondrial membrane potential (Δψm), were quantified. Furthermore, chondrocytes were treated with rotenone (Ro), a specific inhibitor of the MRC, and curcumin (Cur), a mitochondrial protective agent, with the aim of analyzing the relationship between mitochondrial dysfunction and chondrocyte apoptosis. The mitochondria of OA chondrocytes showed apoptosis-associated morphological alterations compared with normal cells. The Δψm and the activity of MRC enzymes were decreased in OA chondrocytes. Moreover, compared with normal chondrocytes, treatment with Ro was able to induce morphological changes reminiscent of the phenotype observed in OA chondrocytes. Additionally, Ro inhibited cellular proliferation, increased the apoptotic rate, and decreased the Δψm and the secretion of type II collagen. Furthermore, Cur could partly reverse the effects caused by treatment with Ro. The present data suggested that mitochondrial function was impaired in OA chondrocytes, resulting in an increased chondrocyte apoptosis and decreased type II collagen secretion. In addition, treatment with Cur protected the mitochondrial function and prevented cartilage degeneration. Collectively, the present results suggested that mitochondrial dysfunction may aggravate cartilage degeneration in the pathogenesis of OA.
Background:Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment.Methods:We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant.Results:The three investigative approaches revealed less degeneration on the therapy sides of the knee joints than the control sides in both the 4- and 6-week groups (P < 0.05), regardless of immobilization. No significant differences were observed between the immobilized and nonimmobilized subgroups (P > 0.05).Conclusions:Therapy involving the intraarticular injection of allogenic MSCs promoted cartilage repair in a rat arthritis model, and 3-day immobility after injection had little effect on this therapy.
Various survival scoring systems have been developed to help surgeons select the best candidates for appropriate therapies in patients with metastatic spinal disease. This study aims to discuss the current status and future directions of scoring systems for the prediction of survival prognosis in these patients. The search terms “spine metastases,” “metastatic spinal disease,” and “metastatic spinal cord compression” were combined with “survival prognosis,” “scoring system,” and “score” to elicit relevant literatures in PubMed and Embase databases. As a result, 159 articles were selected from PubMed, and 246 articles were extracted from Embase. After reviewing each article, we carefully included and analyzed 74 articles about the development and evaluation of scoring systems for predicting survival prognosis in spine metastases. In this review, those scoring systems were stratified into the historic scoring systems and the modern scoring systems on the basis of the proposed time. The historic scoring systems, including the original/revised Tokuhashi scoring system, the Bauer scoring system, the Tomita scoring system, and the Linden scoring system, and the modern scoring systems, such as the Lei scoring system, the Bartels scoring system, the Mizumoto scoring system, the Bollen scoring system, the Rades scoring system, Oswestry Spinal Risk Index, and the Choi risk calculator, were introduced and discussed in this review. Besides, the clinical effectiveness and pitfalls of the existing systems and the future directions of the next generation of scoring systems were also addressed and discussed. We recommended these scoring systems as preferable reference tools to help doctors to select surgical candidates. In patients with long-term life expectancy, radical surgery, such as wide or marginal excision, can be considered in patients with neurological deficits, spine instability, or severe back pain. Besides, with the advancement and improvement of medical technologies, surgical procedures are changing, which can affect surgical indications such as vertebroplasty, minimal invasive surgery, and percutaneous stabilization, which can also be used in patients with spine instability or severe back pain, and do not require much recovery; hence, they can even be used in patients with relative short-term life expectancy. However, the decision about the treatment of patients with metastatic spinal disease is so complicated and should never rely on prognostic scores alone. The final therapeutic decision should be made by interdisciplinary corporations of oncologists, radiologists, and spinal surgeons. Besides, individual intentions should be respected.
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