AP1 can directly interact with the Bmal1 promoter and activate C-C motif chemokine 2 and RANKL transcription in PDLCs, which consequently recruits monocytes to differentiate into osteoclasts, promotes bone remodeling and orthodontic tooth movement.165 In another IDD model induced by abnormal mechanical loading, the intrinsic circadian clock in the intervertebral disc was dampened, and the Bmal1 expression could be partially rescued by RhoA/ROCK pathway (a crucial pathway in mechanotransduction166) inhibition Y-27632 and melatonin.167. The gene discussed is BMAL1; the disease is intervertebral disk degenerative disorder.