PER1 and osteoporosis: For example, Per1 KO in NK cells alters the peak level and timing of the circadian expression of interferon γ (IFN-γ) and cytolytic factors (perforin and granzyme B).34Per1 KD in helper T cells inhibits the synthesis of IFN-γ, IL-2, and TNF-α.35 These cytokines are involved in bone remodeling and osteoporosis.36–38 Furthermore, Per1 depletion indirectly affected Cx3cr1-negative cells as indicated by the decreased number of osteoblasts in the tibiae.