In conclusion, we successfully generated two mouse models (Sp7-Cre; Hdac4fl/fl and Acan-CreERT2; Hdac4fl/fl) with deletion of Hdac4 in Sp7-expressing osteoprogenitors or chondrocytes and revealed that Hdac4 deficiency increases susceptibility to dwarfism, growth plate closures, and osteoporosis progression. This evidence concerns the gene ACAN and osteoporosis.