Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) extracellular vesicles (EVs) are found to be capable of accelerating Osteoarthritis (OA) progression. However, which pathways and which pathogenic EVs subgroups are involved are not defined. In our study we found that there were a higher percentage of TOMM20⁺ EV's within the total synovial fluid EV's from OA patients than from trauma patients as well as increased mtDNA content. This implicates the mitochondria derived EV sub-group - mitochondria derived vesicles (MDVs) as a potential driver in OA. We found with the single-cell data that MDVs may be secreted from IPFP-MSCs with VPS35. Furthermore, these cells were harvested from the body of the OA patient. IPFP-MSC derived MDVs can deliver exogenous mtDNA to chondrocytes by fusing directly, thus inhibiting chondrocyte matrix synthesis, inducing mitochondrial dysfunction, and activating pro-inflammatory signaling cascades in chondrocytes. Protein microarrays showed that MDVs delivered exogenous mtDNA to chondrocytes, which then activated the cGAS-STING pathway and downstream inflammatory mediators (TBK1, NF-κB, TNF-α). Intra-articular MDV injection worsened cartilage degradation and synovitis in OA rats but STING inhibition alleviated them. This study showed that IPFP-MSC-derived MDVs are essential for OA pathogenesis via mtDNA transfer and cGAS-STING pathway activation. These results show how the mitochondria and immune system talk to each other in the joints causing pain and destroying the cartilage, MDVs are new things that can tell us if someone has this disease and help doctors fix it. Pharmacological blockade of the cGAS-STING axis has shown therapeutic potential, providing a dual approach to mitigate mitochondrial stress and innate immune hyperactivation in OA.

Background: Osteosarcoma is a primary bone malignancy with a known bimodal age distribution. However, epidemiological patterns based on precise primary anatomical sites are not well characterized. This population‐based study analyzed the Surveillance, Epidemiology, and End Results (SEER) database to compare the incidence and clinical features of central‐site versus peripheral‐site osteosarcoma across different age groups. Aims: This study aimed to compare the incidence characteristics of peripheral and central‐site osteosarcoma (OS) and to explore the impact of different primary sites on the prognosis of patients with OS. Methods: Patients diagnosed with OS (1975–2019) were selected from the SEER databases. The different primary sites, diagnosis time, and incidence of OS were described statistically. A 1:1 propensity score matching (PSM) was used to adjust for clinical characteristics and treatment. Kaplan–Meier curves were used to compare overall survival and CSS of peripheral and central‐site OS before and after matching. Univariate and multivariate Cox models were used to investigate prognostic factors for CSS in both groups. Results: A total of 3129 patients were included (899/28.73% central‐site OS, 2166/69.22% peripheral‐site OS, 64/2.05% other‐site OS). After PSM, central‐site OS had lower overall survival and CSS than peripheral‐site OS (5‐year overall survival, 0.415 vs. 0.468; 5‐year CSS, 0.454 vs. 0.555). Multivariate analysis revealed that age ( p = 0.010), primary site ( p = 0.039), historical SEER stage (regional, p = 0.012; distant, p < 0.001), histologic grade (grade III, p = 0.014; grade IV, p = 0.009), surgery ( p < 0.001), and radiotherapy ( p = 0.005) were significant factors for CSS. Subgroup analyses adjusting for these factors showed better CSS in peripheral‐site OS patients. Conclusions: The incidence of central‐site OS is lower than that of peripheral‐site OS, while the prognosis of patients with peripheral‐site OS is more favorable than that of patients with central‐site OS. Surgical intervention is a cornerstone in the management of OS and is effective for both central‐site and peripheral‐site OS.

Background This study aimed to compare the incidence characteristics of peripheral and central-site osteosarcoma (OS) and to explore the impact of different primary sites on the prognosis of patients with OS. Methods Patients diagnosed with OS (1975-2019) were selected from the SEER databases. The different primary sites, diagnosis time and incidence of OS were described statistically. A 1:1 propensity score matching (PSM) was used to adjust for clinical characteristics and treatment. Kaplan-Meier curves were used to compare overall survival and CSS of peripheral and central-site OS before and after matching. Univariate and multivariate Cox models were used to investigate prognostic factors for CSS in both groups. Results A total of 3,129 patients were included (899/28.73% central-site OS, 2166/69.22% peripheral-site OS, 64/2.05% other-site OS) . After PSM, central-site OS had lower overall survival and CSS than peripheral-site OS (5-year overall survival, 0.415 vs. 0.468; 5-year CSS, 0.454 vs. 0.555). Multivariate analysis revealed that age (P=0.010), primary site (P=0.039), historical SEER stage (regional, P=0.012; distant, P＜0.001), histologic grade (grade Ⅲ, P=0.014; grade Ⅳ, P=0.009), surgery (P＜0.001), and radiotherapy (P=0.005) were significant factors for CSS. Subgroup analyses adjusting for these factors showed better CSS in peripheral-site OS patients. Conclusions The incidence of central-site OS is lower than that of peripheral-site OS, while the prognosis of patients with peripheral-site OS is more favorable than that of patients with central-site OS. Surgical intervention is a cornerstone in the management of OS and is effective for both central-site and peripheral-site OS.