ECTS Abstracts (2015) 1 P204

Tartrate resistant acid phosphatase 5a - a coupling factor between osteoclast and osteoblast with potential growth factor activity?

Laia Mira Pascual, Christina Patlaka, Pernilla Lång & Göran Andersson


Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Huddinge, Sweden.


Tartrate-resistant acid phosphatase (TRAP) is a phosphatase highly expressed by osteoclasts (OCs). Also osteoblasts (OB)/ osteocytes (OCy) expresses TRAP.1,2 In OC, TRAP is secreted as an enzymatically inactive proenzyme, TRAP5a, that processed by cysteine proteinases forms enzymatically active TRAP5b.3 Conventionally, TRAP 5a has been regarded as a latent pro-form of TRAP 5b with no biological activity. Recently, this view has been challenged with the discovery that TRAP 5a, but not 5b, induces proliferation/differentiation in the mesenchymal stem cells. Also, TRAP overexpression leads to increased OB activity and cortical bone.4 Additionally, TRAP induces proliferation in haematopoietic stem cells i.e. the lineage from where OC precursors are derived. To investigate the role of TRAP 5a on OB and OC we used cell culture, immunohistochemistry, cell cycle and morphological analysis in combination with MC3T3-E1, RAW 264.7 and TRAP overexpressing mice. Addition of TRAP 5a to MC3T3-E1 cells caused an increase in number of cells in S-phase. Moreover, TRAP 5a caused morphological changes consistent with alterations of the cytoskeleton. In addition, elevated levels of circulating monocytes were found in TRAP overexpressing mice. The study was approved by the Stockholm South Animal Ethical Committee (S159/01 and S235/04). Based on these data we suggest that TRAP5a is released into the resorption lacuna and thus could potentially function as a coupling factor between OC-OB to increase OB proliferation and activity. Additionally, we hypothesise that TRAP 5a might increase numbers of OC precursors. This work was funded by Swedish Research Council and funds from Karolinska Institutet.

Disclosure: The authors declared no competing interests. This work was funded by Swedish Research Council K2015-99X-10363-23-4 and funds from Karolinska Institutet e.g. Karolinska Fonder.

References:

1. Solberg, L. B. et al. Calcif. Tissue Int. 94, 510–21 (2014).

2. Solberg, L. B. et al Histochem. Cell Biol. (2014).

3. Ljusberg, J. et al. J Biol Chem 280, 28370–28381 (2005).

4. Gradin, P. et al Cells. Tissues. Organs (2012).

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