NF-κBp50/p52 double knockout(dKO)and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism.In contrast,Op/Op mice,which form few osteoclasts,and Src KO mice,which have osteoclasts with defective resorptive function,are osteopetrotic,but they are not dwarfed.Here,we compared the morphologic features of long bones from p50/p52 dKO,RANK KO,Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths.We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone.This growth plate abnormality disappears when animals become older,but their dwarfism persists.Op/Op or Src KO mice have relatively normal growth plate morphology.In-situ hybridization study of long bones from p50/p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes.Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9,markers for proliferative chondrocytes,but RANKL reduced the number of type 10collagen-expressing hypertrophic chondrocytes.Thus,RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice. NF-κBp50 / p52 double knockout (dKO) and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op / Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function , are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50 / p52 dKO, RANK KO, Op / Op and Src KO mice to attempt to explain the differences in their long bone lengths.We found that growth plates in p50 / p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op / Sr or KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from p50 / p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-e xpressing chondrocytes. Treatment of micro-mass chondrocytes cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK / NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.