Osteoarthritis (OA) is a worldwide chronic disease that can cause severe inflammation to damage the surrounding tissue and cartilage. There are many different factors that can lead to osteoarthritis, but abnormally progressed programmed cell death is one of the most important risk factors that can induce osteoarthritis. Prior studies have demonstrated that programmed cell death, including apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and cuproptosis, has a great connection with osteoarthritis. In this paper, we review the role of different types of programmed cell death in the generation and development of OA and how the different signal pathways modulate the different cell death to regulate the development of OA. Additionally, this review provides new insights into the radical treatment of osteoarthritis rather than conservative treatment, such as anti-inflammation drugs or surgical operation.

Osteoarthritis (OA) is a principal cause of aches and disability worldwide. It is characterized by the inflammation of the bone leading to degeneration and loss of cartilage function. Factors, including diet, age, and obesity, impact and/or lead to osteoarthritis. In the past few years, OA has received considerable scholarly attention owing to its increasing prevalence, resulting in a cumbersome burden. At present, most of the interventions only relieve short-term symptoms, and some treatments and drugs can aggravate the disease in the long run. There is a pressing need to address the safety problems due to osteoarthritis. A disintegrin-like and metalloprotease domain with thrombospondin type 1 repeats (ADAMTS) metalloproteinase is a kind of secretory zinc endopeptidase, comprising 19 kinds of zinc endopeptidases. ADAMTS has been implicated in several human diseases, including OA. For example, aggrecanases, ADAMTS-4 and ADAMTS-5, participate in the cleavage of aggrecan in the extracellular matrix (ECM); ADAMTS-7 and ADAMTS-12 participate in the fission of Cartilage Oligomeric Matrix Protein (COMP) into COMP lyase, and ADAMTS-2, ADAMTS-3, and ADAMTS-14 promote the formation of collagen fibers. In this article, we principally review the role of ADAMTS metalloproteinases in osteoarthritis. From three different dimensions, we explain how ADAMTS participates in all the following aspects of osteoarthritis: ECM, cartilage degeneration, and synovial inflammation. Thus, ADAMTS may be a potential therapeutic target in osteoarthritis, and this article may render a theoretical basis for the study of new therapeutic methods for osteoarthritis.

Metabolic reprogramming is of great significance in the progression of various cancers and is critical for cancer progression, diagnosis, and treatment. Cellular metabolic pathways mainly include glycolysis, fat metabolism, glutamine decomposition, and oxidative phosphorylation. In cancer cells, reprogramming metabolic pathways is used to meet the massive energy requirement for tumorigenesis and development. Metabolisms are also altered in malignant osteosarcoma (OS) cells. Among reprogrammed metabolisms, alterations in aerobic glycolysis are key to the massive biosynthesis and energy demands of OS cells to sustain their growth and metastasis. Numerous studies have demonstrated that compared to normal cells, glycolysis in OS cells under aerobic conditions is substantially enhanced to promote malignant behaviors such as proliferation, invasion, metastasis, and drug resistance of OS. Glycolysis in OS is closely related to various oncogenes and tumor suppressor genes, and numerous signaling pathways have been reported to be involved in the regulation of glycolysis. In recent years, a vast number of inhibitors and natural products have been discovered to inhibit OS progression by targeting glycolysis-related proteins. These potential inhibitors and natural products may be ideal candidates for the treatment of osteosarcoma following hundreds of preclinical and clinical trials. In this article, we explore key pathways, glycolysis enzymes, non-coding RNAs, inhibitors, and natural products regulating aerobic glycolysis in OS cells to gain a deeper understanding of the relationship between glycolysis and the progression of OS and discover novel therapeutic approaches targeting glycolytic metabolism in OS.