Differential expression and activity of tissue-nonspecific alkaline phosphatase (TNAP) in rat odontogenic cells in vivo

Among the four existing isoforms of alkaline phosphatase (AP), the present study is devoted to tissue-nonspecific alkaline phosphatase (TNAP) in miner alized dental tissues. Northern blot analysis and measurements of phosphohy drolase activity on microdissected epithelium and ectomesenchyme, in situ h ybridization, and immunolabeling on incisors confirmed that the AP active i n rodent teeth is TNAP. Whereas the developmental pattern of TNAP mRNA and protein and the previously described activity were similar in supra-amelobl astic and mesenchymal cells, they differed in enamel-secreting cells, the a meloblasts. As previously shown for other proteins involved in calcium and phosphate handling in ameloblasts, a biphasic pattern of steady-state TNAP mRNA levels was associated with additional variations in ameloblast TNAP pr otein levels during the cyclic modulation process. Although the association of TNAP upregulation and the initial phase of biomineralization appeared t o be a basic feature of all mineralized tissues, ameloblasts (and to a less er extent, odontoblasts) showed a second selectively prominent upregulation of TNAP mRNA/protein/activity during terminal growth of large enamel cryst als only, i.e., the maturation stage. This differential expression/activity for TNAP in teeth vs bone may explain the striking dental phenotype vs bon e reported in hypophosphatasia, a hereditary disorder related to TNAP mutat ion.