Osteoarthritis (OA) is a degenerative disease linked to aging and obesity. The global aging population has led to an increasing number of OA patients, imposing a significant economic burden on society. Traditional drugs treatment methods often fail to achieve satisfactory outcomes. With the rapid advancement of nanomaterial delivery systems, numerous studies have focused on utilizing nanomaterials as carriers to achieve efficient OA treatment by effectively loading and delivering bioactive ingredients (e.g., drugs, nucleic acids) tailored to the unique pathological conditions, such as the weakly acidic microenvironment of synovial fluid in OA patients. This review highlights the latest advancements in the use of pH-responsive nanoparticles for OA treatment, emphasizing the principle of targeted drug delivery leveraging the acidic microenvironment of inflamed joints. It further discusses the composition, synthesis, response mechanism, target selection, application, and recent research findings of nanoparticles, while also addressing the challenges and future directions in this promising field.

Osteoarthritis (OA), known as one of the most common types of aseptic inflammation of the musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular and molecular changes including senescence, inflammatory alterations, and subsequent cartilage defects, OA eventually leads to a series of adverse outcomes such as pain and disability. CRISPR-Cas-related technology has been proposed and explored as a gene therapy, offering potential gene-editing tools that are in the spotlight. Considering the genetic and multigene regulatory mechanisms of OA, we systematically review current studies on CRISPR-Cas technology for improving OA in terms of senescence, inflammation, and cartilage damage and summarize various strategies for delivering CRISPR products, hoping to provide a new perspective for the treatment of OA by taking advantage of CRISPR technology.

Low back pain (LBP) is the leading cause of disability in the elderly. Intervertebral disc degeneration (IDD) was considered as the main cause for LBP. Degeneration of cartilaginous endplate was a crucial harmful factor during the initiation and development of IDD. Oxidative stress was implicated in IDD. However, the underlying molecular mechanism for the degeneration of cartilaginous endplate remains elusive. Herein, we found that oxidative stress could induce apoptosis and autophagy in endplate chondrocytes evidenced by western blot analysis, flow cytometry, immunofluorescence staining, GFP‐LC3B transfection, and MDC staining. In addition, we also found that the apoptosis of endplate chondrocytes was significantly increased after the inhibition of autophagy by bafilomycin A1 shown by flow cytometry. Furthermore, mTOR pathway upstream autophagy was greatly suppressed suggested by western blot assay. In conclusion, our study strongly revealed that oxidative stress could increase autophagy and apoptosis of endplate chondrocytes in intervertebral disc. The increase of autophagy activity could prevent endplate chondrocytes from apoptosis. The autophagy in endplate chondrocytes induced by oxidative stress was mTOR dependent. These findings might shed some new lights on the mechanism for IDD and provide new strategies for the treatments of IDD.

Articular cartilage (AC) damage is quite common, but due to AC’s poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-β3 (TGF-β3) to enhance cartilage tissue formation and ghrelin synergy TGF-β to significantly enhance the chondrogenic differentiation. The hydrogel and microspheres were characterized in vitro, and the biocompatibility of the system was verified. Double emulsion solvent extraction technology (w/o/w) is used to encapsulate TGF-β3 and ghrelin into microspheres, and these microspheres are encapsulated in a hydrogel to continuously release TGF-β3 and ghrelin. According to the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) in vitro, the concentrations of the two growth factors were optimized to promote cartilage regeneration.

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

Osteoarthritis refers to a degenerative disease with joint pain as the main symptom, and it is caused by various factors, including fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments can only delay the progression of osteoarthritis, and patients may need joint replacement eventually. As a class of organic compound molecules weighing less than 1000 daltons, small molecule inhibitors can target proteins as the main components of most drugs clinically. Small molecule inhibitors for osteoarthritis are under constant research. In this regard, by reviewing relevant manuscripts, small molecule inhibitors targeting MMPs, ADAMTS, IL-1, TNF, WNT, NF-κB, and other proteins were reviewed. We summarized these small molecule inhibitors with different targets and discussed disease-modifying osteoarthritis drugs based on them. These small molecule inhibitors have good inhibitory effects on osteoarthritis, and this review will provide a reference for the treatment of osteoarthritis.