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Osteoarthritis (OA) poses a significant burden for countless individuals, inflicting relentless pain and impairing their quality of life. Although traditional treatments for OA focus on pain management and surgical interventions, they often fall short of addressing the underlying cause of the disease. Fortunately, emerging biomaterial-based scaffolds offer hope for OA therapy, providing immense promise for cartilage regeneration in OA. These innovative scaffolds are ingeniously designed to provide support and mimic the intricate structure of the natural extracellular matrix, thus stimulating the regeneration of damaged cartilage. In this comprehensive review, we summarize and discuss current landscape of biomaterial-based scaffolds for cartilage regeneration in OA. Furthermore, we delve into the diverse range of biomaterials employed in their construction and explore the cutting-edge techniques utilized in their fabrication. By examining both preclinical and clinical studies, we aim to illuminate the remarkable versatility and untapped potential of biomaterial-based scaffolds in the context of OA. Thetranslational potential of this article: By thoroughly examining the current state of research and clinical studies, this review provides valuable insights that bridge the gap between scientific knowledge and practical application. This knowledge is crucial for clinicians and researchers who strive to develop innovative treatments that go beyond symptom management and directly target the underlying cause of OA. Through the comprehensive analysis and multidisciplinary approach, the review paves the way for the translation of scientific knowledge into practical applications, ultimately improving the lives of individuals suffering from OA and shaping the future of orthopedic medicine.

Osteoarthritis (OA) is a chronic degenerative disease afflicting millions globally. Despite the development of numerous pharmacological treatments for OA, a substantial unmet need for effective therapies persists. The RANK/RANKL signaling pathway has emerged as a promising therapeutic target for OA, owing to its pivotal role in regulating osteoclast differentiation and activity. In this comprehensive review, we aim to elucidate the relevant mechanisms of OA mediated by RANK/RANKL signaling, including bone remodeling, inflammation, cartilage degradation, osteophyte formation, and pain sensitization. Furthermore, we discuss and summarize the cutting-edge strategies targeting RANK/RANKL signaling for OA therapy, encompassing approaches such as gene-based interventions and biomaterials-aided pharmacotherapy. In addition, we highlight the prevailing challenges associated with pharmacological OA treatments and explore potential future directions, approached through a clinical-translational lens.

Abstract Background This retrospective study aimed to introduce a novel method for simultaneous Y-shape osteotomy combined with subtalar arthrodesis for calcaneus malunion and to evaluate the feasibility of this method. Methods We retrospectively analysed the clinical and imaging data of 11 patients with calcaneus malunion treated using Y-shape osteotomy and subtalar arthrodesis who were admitted to our hospital from June 2018 to October 2020. The patients included 9 males and 2 females aged from 24 to 69 years old, with an average age of 42.18 years. The clinical and radiological results were assessed with the Visual Analogue Scale (VAS) pain score and American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. In addition, functional recovery and general quality of life were evaluated using the 12-Item Short-Form Survey (SF-12). Results All radiological parameters were significantly improved at the last follow-up, with increases of 14.37°, 9.18°, and 4.51 mm in the Böhler’s angle, calcaneal pitch angle, and talocalcaneal height, respectively, and decreases of 6.39 mm and 6.18° in the calcaneal width and Hindfoot alignment angle (p

Charcot neuroarthropathy (CN) is a chronic, destructive, and painless damage of the skeletal system that affects the life quality of patients. CN, with an unclear mechanism, is characterized with invasive destruction of bones and a serious abnormality of bone metabolism. Unfortunately, development of an effective prevention and treatment strategy for CN is still a great challenge. Of note, recent studies providing an insight into the molecular mechanisms of bone metabolism and homeostasis have propelled development of novel CN therapeutic strategies. Therefore, this review aims to shed light on the pathogenesis, diagnosis, and treatment of CN. In particular, we highlight the eminent role of the osteoprotegerin (OPG)-receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL) system in the development of CN. Furthermore, we summarize and discuss the diagnostic biomarkers of CN as well as the potential pharmacological mechanisms of current treatment regimens from the perspective of bone metabolism. We believe that this review will enhance the current state of knowledge on the diagnosis, prevention, and therapeutic efficacy of CN.

With the markedly increased diagnosis and incidence of cancer in the population, tumor bone metastasis has become a frequent event in tumor patients. Healthy bone integrity is maintained by a delicate balance between bone formation and bone resorption. Unfortunately, many tumors, such as prostate and breast, often metastasize to the bone, and the alterations to the bone homeostasis can particularly favor tumor homing and consequent osteolytic or osteoblastic lesions. Receptor activator of NF-κB ligand (RANKL), its receptor RANK, and osteoprotegerin (OPG) are involved in the regulation of the activation, differentiation, and survival of osteoclasts, which play critical roles in bone metastasis formation. High rates of osteoclastic bone resorption significantly increase fracture risk, cause severe bone pain, and contribute to homing tumor cells in bone and bone marrow. Consequently, suppression of the RANK/RANKL/OPG system and osteoclastic activity can not only ameliorate bone resorption but may also prevent tumor bone metastases. This review summarizes the important role of the RANK/RANKL/OPG system and osteoclasts in bone homeostasis and its effect on tumor bone metastasis and discusses therapeutic strategies based on RANKL inhibition.

Rheumatoid arthritis (RA) has a high incidence and adverse effects on patients, thus posing a serious threat to people’s life and health. However, the underlying mechanisms regarding the development of RA are still elusive. Herein, we aimed to evaluate the RA-associated molecular mechanisms using the scRNA-seq technique. We used the GEO database to obtain scRNA-seq datasets for synovial fibroblasts (SFs) from RA cases, and the genes were then analyzed using principal component analysis (PCA) and T-Stochastic Neighbor Embedding (TSNE) analyses. Bioinformatics evaluations were carried out for asserting the highly enriched signaling pathways linked to the marker genes, and the key genes related to RA initiation were further identified. According to the obtained results, 3 cell types (0, 1, and 2) were identified by TSNE and some marker genes were statistically upregulated in cell type 1 than the other cell types. These marker genes predominantly contributed to extracellular matrix (ECM) architecture, collagen-harboring ECM, and ECM structural components, and identified as enriched with PI3K/AKT signaling cascade. Notably, fibronectin-1 (FN-1) has been identified as a critical gene that is strongly linked to the development of SFs and has enormous promise for regulating the onset of RA. Moreover, such an investigation offers novel perspectives within onset/progression of RA, suggesting that FN-1 may be a key therapeutic target for RA therapies.

The COVID-19 pandemic caused by the severe acute coronavirus disease 2 (SARS-CoV-2) virus represents an ongoing threat to human health and well-being. Notably, many COVID-19 patients suffer from complications consistent with osteoporosis (OP) following disease resolution yet the mechanistic links between SARS-CoV-2 infection and OP remain to be clarified. The present study was thus developed to explore the potential basis for this link by employing transcriptomic analyses to identify signaling pathways and biomarkers associated with OP and SARS-CoV-2. Specifically, a previously published RNA-sequencing dataset (GSE152418) from Gene Expression Omnibus (GEO) was used to identify the differentially expressed genes (DEGs) in OP patients and individuals infected with SARS-CoV-2 as a means of exploring the underlying molecular mechanisms linking these two conditions. In total, 2,885 DEGs were identified by analyzing the COVID-19 patient dataset, with shared DEGs then being identified by comparison of these DEGs with those derived from an OP patient dataset. Hub genes were identified through a series of bioinformatics approaches and protein-protein interaction analyses. Predictive analyses of transcription factor/gene interactions, protein/drug interactions, and DEG/miRNA networks associated with these DEGs were also conducted. Together, these data highlight promising candidate drugs with the potential to treat both COVID-19 and OP.

This paper proposes a framework for examining the interaction between stock market volatilities and economic uncertainty shocks, aiming to understand better the influence of economic uncertainty shocks on the Chinese stock market. The major empirical results include the followings. First, the economic policy uncertainty shocks push the Chinese stock volatility up, increasing the market risk. A 1-standard-deviation shock of economic policy uncertainty will enhance the stock volatility of the two composite indices by approximately 7% in 12 months. Second, the stock volatility reacted more intensely to fiscal and monetary economic policy uncertainty shocks, with a 1-standard-deviation shock that can enhance the stock volatility of the two composite indices by more than 10% in 12 months. Third, different stock indices exhibit different patterns of cumulative impulse responses, and the reaction of the volatility of the SSE real estate index to economic policy uncertainty shocks is more significantly intense than other indices. Besides, we have proved the robustness of empirical results by reestimating the models with a lag order of 2. Overall, our research results can provide policy and managerial insights for the sustainable development of the Chinese stock market and beyond.