Timp-1, -2 and -3 show coexpression with gelatinases A and B during mouse tooth morphogenesis

Matrix metalloproteinases (MMPs) have been implicated in tissue remodelling and in regulation of cell-matrix interactions during organ development. Th e activity of MMPs is regulated by members of the TIMP (tissue inhibitors o f metalloproteinase) family. We analyzed by in situ hybridization the expre ssion of gelatinase A (MMP-2) and gelatinase B (MMP-9) as well as Timp-1, - 2 and -3 during different stages of mouse tooth development. Gene expressio n was generally found in mesenchymal tissues except for Timp-3, which also was found in dental epithelial cells. During early tooth development, gelat inase A and Timp-2 were widely expressed in the branchial arch, while gelat inase B and Timp-1 and Timp-3 expression showed clear association with epit helial morphogenesis and was restricted to the mesenchyme at the tip of the growing tooth bud. Gelatinase A and Timp-1 showed transient expression in secretory odontoblasts at the time of basement membrane degradation, while Timp-2 expression continued throughout the dental papilla. At the time of t ooth eruption, Timp-3 was expressed in most dental epithelial cells except secretory ameloblasts, and gelatinase B was intensely expressed in osteocla sts in the jaw bone. The exact co-localization of gelatinase A and Timp-1 i n secretory odontoblasts, and the correlation between gelatinase B and Timp -3 during bone resorption may indicate interaction of the proteins during d egradation of the basement membrane and in the control of ECM turnover in c onnection with tooth eruption.