C57bl 6j mice

C57BL/6J mice were purchased from GemPharmatech Co., Ltd (Nanjing, China) and housed under specific pathogen-free conditions. Experiments were performed with male animals at 6–8 weeks of age under ethical conditions approved by the Institutional Animal Care and Use Committee of The Third Affiliated Hospital of Sun Yat-sen University.
For Con A-induced fulminant hepatitis model, a single dose of Con A (Sigma Aldrich, St. Louis, MO) was administrated at 15 or 20 mg/kg (only for survival analysis) through the tail vein. PBS or 1 × 10⁶ hWJ-MSCs suspended in 200 μL PBS were transplanted intravenously (i.v) 30 min after Con A administration. Liver tissues were collected at indicated time point, and serum was collected at various time points for further analysis.
For live imaging, cells were labeled with 10 µg/ml 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR; AAT Bioquest, USA) for 15 min at 37 °C according to the manufacturer’s instructions. The DiR-labeled MSCs were washed twice with PBS and transplanted into mouse i.v 30 min after Con A administration. Live imaging was conducted at different time points under anesthesia using Xenogen IVIS Lumina II.

All male C57BL/6J mice were purchased (GemPharmatech Co., Ltd) and kept housed in the experimental animal center at the Medical School of Nanjing University. DMM operation was used as the murine experimental OA model as previously described,^[44
] in which the medial meniscus was destabilized by transecting the medial meniscotibial ligament.
To assess the effect of ctr‐exo or inf‐exo on synovitis and cartilage degeneration, exosomes resuspended in saline were sterilized with a 0.22 µm filter and intra‐articularly injected into joint cavities (20 µg per mouse at each injection). To evaluate the therapeutic potential of HIF1A inhibition against OA, PX‐478 (B6004, APExBIO, Houston, USA) was administrated via intraperitoneal injection to sham or DMM mice PX‐478 (100 mg kg⁻¹) every other day. Mice injected with an equal volume of valine were used as controls in each experiment.
Mice were euthanized by intraperitoneal injection of sodium pentobarbital at an overdose. Experimental protocols for animal experiments were approved by the Ethics Committee and the Institutional Animal Care and Use Committee of the Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School.

The C57BL/6J mice (female, 5 months old, 3 for each group) were purchased from the GemPharmatech company. The animals were kept in a specific pathogen free (SPF) environment with a 12:12 light-dark cycle with free access to food and water. Animal experiments were performed according to the NIH Guide for the Care and Use of Laboratory animal. All procedures were approved by the ethical committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.
Isoflurane was deployed for anesthesia, and a stereotaxic instrument (RWD life science, China) was used to locate the hippocampal CA3 region (coordinates: –2.8 mm anteroposterior, ± 20.5 mm mediolateral, and –3 mm dorsoventral). Before injections, lentiviral vectors were diluted with sterile phosphate-buffered saline (PBS) to achieve a titer of 1 × 10⁸ TU/ml and shortly stored on ice. Each mouse was transcranially injected with 2 μl Lvv-GFP-CSP α^WT, Lvv-GFP-CSP α^C128Y, or Lvv-GFP (vector) bilaterally using a 10-μl syringe over 5 min. The needle remained in place for 5 min after complete injection and then was slowly removed. Two months after stereotactic injection, the mice were sacrificed. One hemisphere was fixed in 4% paraformaldehyde (PFA), and the other hemisphere was fixed in the 2.5% glutaraldehyde.

All animal procedures were conducted according to protocols approved by the Institutional Animal Care and Use Committee of the Medical School of Southeast University. Adult male (6–8 weeks) C57BL/6 J mice (GemPharmatech, Nanjing, China) kept under a constant temperature and 12:12 h light: dark cycles were used. HECTD1^flox/flox mice (HECTD1^f/f, C57BL/6 J background) were generated and maintained at GemPharmatech (Nanjing, China). Food and water were provided ad libitum.