Butorphanol Tartrate Mitigates Cellular Senescence Against Tumor Necrosis Factor –α (Tnf-Α) in Human HC-A Chondrocytes

Aging is an important risk factor for osteoarthritis (OA). Butorphanol is a preoperative sedative and analgesic that possesses anti-inflammatory activity. However, the effect of butorphanol on OA has not been reported. Here we aimed to explore the effect of butorphanol tartrate on the cellular senescence of human chondrocyte-articular (HC-A) cells in response to tumor necrosis factor-α (TNF-α) stimulation. Butorphanol tartrate attenuated the TNF-α-caused cellular senescence of HC-A cells, with decreased positive senescence-associated-β-galactosidase (SA-β-gal) staining and elevated telomerase activity. Butorphanol tartrate prevented TNF-α-caused cell cycle arrest in the G0/G1 phase in HC-A cells and decreased p21 expression. The TNF-α-induced production of interleukin (IL)-6 and IL-8 in HC-A cells were mitigated by butorphanol tartrate. In addition, butorphanol tartrate reduced p-NF-κB p65/total p65 and p-STAT3/STAT3 ratios in HC-A cells cultured with TNF-α. Taken together, butorphanol tartrate protected HC-A cells from TNF-α-caused cellular senescence through inactivation of NF-κB and STAT3. These results imply that butorphanol tartrate might be used as a potential agent for the treatment of aging-related OA.