Figure 4

SOC osteogenic tissue arises from Col2 + chondrocytes (A–I’) Lineage trace analysis of Col2-Cre ERT2 mice reveals that most cells in the epiphysis express TOM. As cells become hypertrophic (MMP13) (A,E) they continue to express TOM. Eventually, hypertrophic cells surround unlabeled TOM + cells (I). TOM + cells do, however, co-label with osteogenic markers such as ALP (F,J), DMP1 (G,K) and COL1 (H,L) at P9 and P10 during SOC formation. (M,N) Later stage, 12 week (12 W) Col2-Cre ERT2 mice have SOCs which contain a large amount of TOM + cells as well as those colabeled with OSX (M; arrow) and ALP (N; arrow). (O) Methimazole treated Col2-Cre ERT2 mice did not form an SOC and only expressed low levels of DMP1 by P14. The SOC is usually well into its formation at this time point. Yellow boxes enlarge related regions, “ ‘ ” denotes enlarged region (e.g., A’). Large Scale bars are 100 μm and small scale bars are 200 μm.