Osteocalcin is incompletely spliced in non-osseous tissues

Osteocalcin (OC) is known to be a bone tissue-specific protein, expression of which is believed to be controlled by the OC promoter. In this communica tion, we provided evidence to demonstrate that tissue-specific expression o f OC was also regulated at the RNA splicing level. We identified incomplete ly spliced variants of human OC mRNA, which retain one or more introns duri ng RNA spicing, existing dominantly in non-osseous organs. Northern blot an alysis identified two OC RNA transcripts expressed in normal human tissues. but the expression level of the transcripts varied between the tissues. Mo st non-osseous tissues expressed transcripts with higher molecular weight, prominent in ovary, kidney, pancreas, spleen, thymus, prostate, and testis, than the expected size of OC mRNA as seen in bone marrow. RT-PCR analysis identified up to six OC transcripts in most tissues tested except bone marr ow. Sequence analysis showed that four of five RNA variants contained intro n 1 in common and the dominant one contained all three introns. MG63, an os teoblastic osteosarcoma cell, expressed only the completely-spliced form of OC, whereas incompletely spliced RNA was dominant in most prostate tumor c ells. Combined study of it? situ hybridization and immunohistochemistry rev ealed that OC RNA was highly expressed in prostate tumor epithelial cells w hile only very low levels of protein were detected, which confirms that the re are OC RNA variants in non-osseous tissues. In conclusion, we demonstrat ed that OC mRNA is also expressed in several non-osseous tissues. However, only bone preferentially underwent the complete splicing event of all three introns. The function of other splicing variants of OC mRNA needs to be fu rther investigated. (C) 2001 Published by Elsevier Science B.V. All rights reserved.