Our findings reveal critical roles of HB‐EGF in regulating proliferation and differentiation of osteoblasts, chondrocytes, and BMSC cultures in autocrine and/or paracrine manners and elucidate the mechanisms by which HB‐EGF executes its functions in skeletal growth and in pathogenesis of osteoarthritis. This evidence concerns the gene HBEGF and osteoarthritis.