Dermo1‐Cre; HB‐EGFf/f mice only showed a modest increase in bone mass, whereas Dermo1‐HB‐EGF mice developed progressive chondrodysplasia, chondroma, osteoarthritis‐like joint defects, and loss of bone mass and density, which were alleviated by treatment with EGFR inhibitor AG1478. Here, TWIST2 is linked to osteoarthritis.