**4. Materials and Methods**

#### *4.1. Human Articular Chondrocyte (HAC) Cultures*

The human articular chondrocyte (HAC) cell line was purchased from Lonza Walkersville Inc. (8F3339, LONZA, MD, USA). The HAC cells were cultured in Dulbecco Modified Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS), 100 IU/mL penicillin, and 100 μg/mL streptomycin at 37 ◦C in a humidified atmosphere of 5% CO2.

#### *4.2. Cell Viability Assay*

Cell viability was measured using Counting Kit-8 (CCK-8 assay). A total of 10,000 HAC cells per well were cultured in 96-wells cell culture plate and then incubated for 48 h at 37 ◦C. After that, HAC cells were cultured in 200 μL culture medium with 7 rh (6.9 nM or 13.8 nM) or co-cultured with

7 rh and IL-1β (10 ng/mL) in 5% CO2 for 3h. Then, 10 μL of CCK-8 reagent (E-CK-A361, Elabscience, Houston, TX, USA) was added and the optical density at 450 nm was measured using a multifunction microplate reader (Synergy H1, BioTek, Winooski, VT, USA) after incubation for 2 h at 37 ◦C.
