Mechanical unloading or Piezo1 inactivation disrupts this balance, leading to excessive activation of the Ccl2-Lcn2 autocrine loop in BMMSCs (because of lower Klf2 expression) and enhanced bone marrow adipogenesis, which in turn contributes to aging- or obesity-related skeletal and/or metabolic disorders. Here, KLF2 is linked to obesity due to melanocortin 4 receptor deficiency.