Knee osteoarthritis (OA) is a degenerative disease that impairs joint function. Adipose-derived stem cells (ADSCs) are promising for therapy due to their regenerative potential, particularly when cultured as spheroids to enhance paracrine activity. However, conventional plate-based spheroid culture faces challenges such as scalability limits, retrieval difficulties, excessive enlargement, and necrotic core formation, all of which may compromise therapeutic efficacy. An optimized, scalable method is therefore required for clinical application. This study aimed to establish a spheroid culture protocol using the SphereRing (R) device with methylcellulose (MC) to regulate spheroid size, improve viability, and enhance secretion of therapeutic factors including exosomes and interleukin-10 (IL-10). ADSCs were cultured in SphereRing (R) with 0.5-1 % MC for 3 days, and spheroid size, morphology, viability, and secretory profiles were assessed. Spheroids cultured with 0.75 % MC exhibited the most uniform size distribution, higher circularity, reduced necrotic core formation, and significantly greater viability compared to untreated controls. Moreover, IL-10 and exosome secretion were markedly increased in the 0.75 % MC group. Patient-derived ADSCs showed comparable improvements. MC-treated spheroids also maintained superior viability after exposure to synovial fluid, simulating intra-articular conditions. These findings suggest that incorporating MC into the SphereRing (R) system enables scalable and uniform spheroid production, establishing a clinically relevant platform for ADSC-based therapy in knee OA with potential to improve treatment consistency and outcomes.
Although elevated soluble uric acid (SUA) levels enhance the production of IL-1β in macrophages stimulated with monosodium urate (MSU) crystals, the underlying mechanism remains unelucidated. The aim of this study was to examine the effects of SUA on inflammatory response-related gene expression in lipopolysaccharide-primed and MSU crystal-stimulated macrophages using mouse macrophage-like J774.1 cells. Differential gene expression in SUA-pretreated and untreated group cells was analyzed by RNA sequencing and quantitative reverse transcription-polymerase chain reaction. SUA upregulated the genes related to pro-inflammatory reactions and downregulated those related to anti-inflammatory reactions. SUA also upregulated M1 pro-inflammatory macrophage-related genes and enhanced mRNA expression of CD44 responsible for phagocytosis of MSU crystals. These results suggest that SUA enhances gouty inflammation via promoting the expression of genes related to pro-inflammatory reactions, polarization toward the M1 phenotype, and MSU crystal phagocytosis in macrophages. Enhanced expression of the transcription factor genes Nfkb1 and Stat1 may underlie the SUA-induced M1 polarization and resulting enhancement of inflammasome activation and IL-1β transcription.
We analytically derive the secular changes of the orbital parameters, i.e., energy, angular momentum, and Carter constant, for general bound orbits in Kerr spacetime, at leading order in the mass ratio, through the 6th post-Newtonian (6PN) order and the 16th order in orbital eccentricity. We validate the formulas against high-precision numerical Teukolsky results and quantify how eccentricity affects both the achievable accuracy and the PN convergence. We then construct and test a simple “hybrid” approximation that combines different PN and eccentricity truncations to retain accuracy at reduced computational cost. We also assess the performance of exponential resummation at higher PN orders. These results provide building blocks for fast, (analytic) adiabatic inspiral and waveform models for extreme mass ratio inspirals relevant to space-based detectors such as the Laser Interferometer Space Antenna (LISA).
Steroid-associated osteonecrosis of the femoral head (SONFH) is closely related to ischemia after corticosteroid treatment as well as the subsequent inflammatory response and oxidative stress. This study examined the temporal and spatial expression of high mobility group box 1 (HMGB1) and peroxiredoxin 4 (PRDX4) in SONFH lesions using immunohistochemistry. Tissue samples from SONFH patients undergoing total hip arthroplasty were compared with those from osteoarthritis (OA) controls. The expression of PRDX4 was significantly reduced in SONFH and was inversely correlated with the oxidative DNA damage marker 8-Hydroxy-2'-deoxyguanosine (8-OHdG). Notably, PRDX4 is strongly expressed in osteoblasts and chondrocytes within callus tissue at the necrotic-viable bone interface, implicating its role in promoting repair through the suppression of oxidative stress. In contrast, most SONFH cases exhibit nuclear-to-cytoplasmic translocation of HMGB1, consistent with its function as a damage-associated molecular pattern (DAMP) that drives inflammatory responses. These findings indicate that HMGB1 acts as an inflammatory mediator during the early phase of SONFH, whereas PRDX4 functions as an oxidative stress regulator during the repair process. Together, these molecules appear to act in a complementary manner to orchestrate the transition from inflammation to tissue regeneration. Their expression dynamics may serve as potential factors for disease progression and reparative activity, while therapeutic strategies targeting HMGB1 signaling or augmenting the expression of PRDX4 may represent promising avenues for intervention.
Periodontitis is a chronic non-communicable inflammatory disease in which oxidative stress plays an important role in tissue destruction and alveolar bone loss. Excessive production of reactive oxygen species disrupts redox homeostasis, activates inflammatory signaling pathways, and promotes regulated cell death processes such as pyroptosis and ferroptosis. The Nrf2/Keap1 pathway is a key regulator of antioxidant defense and cellular adaptation to redox imbalance. Impaired Nrf2 signaling has been associated with enhanced oxidative injury, NF-κB and NLRP3 inflammasome activation, osteoclast-driven bone resorption, and reduced regenerative capacity in periodontal tissues. Experimental studies suggest that Nrf2 activation can restore the redox balance and attenuate inflammation and bone destructive responses in a periodontal model. Moreover, therapeutic approaches involving phytochemicals, microbial-derived metabolites, and redox-responsive biomaterials have been reported to influence Nrf2-related signaling in experimental settings. However, the majority of the available evidence is derived from in vitro or animal studies, and the relevance of these findings to clinical periodontitis remains to be established. This review summarizes the current advances linking oxidative stress, redox signaling, cell death pathways, and bone remodeling with Nrf2 dysfunction in periodontitis and outlines the key mechanistic insights while highlighting the existing knowledge gaps.
