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Secreted Tartrate-Resistant Acid Phosphatase 5b is a Marker of Osteoclast Number in Human Osteoclast Cultures and the Rat Ovariectomy Model

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Abstract

Purpose:

To study the effects of estrogen withdrawal on osteoclast number and osteoclast activity in the rat ovariectomy (OVX) model.

Methods:

We first cultured human CD34+ osteoclast precursor cells on bovine bone slices, allowing them to differentiate into mature resorbing osteoclasts. Secreted tartrate-resistant acid phosphatase 5b (TRACP 5b) and C-terminal cross-linked telopeptides of type I collagen (CTX) were determined from the culture medium. TRACP 5b correlated strongly with osteoclast number and CTX with osteoclast activity, facilitating their subsequent use in the rat OVX model. An 8 week OVX study was then performed including sham-operated rats receiving vehicle, OVX rats receiving vehicle, and OVX rats receiving 10 μg/kg/day 17β-estradiol (E2). Trabecular bone parameters were determined from the tibial metaphysis using peripheral quantitative computed tomography and histomorphometry. Osteoclast number was normalized with bone perimeter (N.Oc/B.Pm) and tissue area (N.Oc/T.Ar, indicating absolute number of osteoclasts). TRACP 5b and CTX were determined from fasting serum samples.

Results:

Trabecular bone parameters indicated substantial bone loss after OVX that was prevented by E2. N.Oc/B.Pm increased after OVX, while N.Oc/T.Ar and TRACP 5b decreased, and TRACP 5b correlated strongly with N.Oc/T.Ar. However, CTX values increased after OVX, and the “resorption index” CTX/TRACP 5b showed more substantial changes than either CTX or TRACP 5b alone.

Conclusion:

These results show that TRACP 5b is a reliable marker of osteoclast number, and the index CTX/TRACP 5b is a useful parameter in rat OVX model. The high elevation of CTX/TRACP 5b values by OVX demonstrates that estrogen withdrawal generates high activity of osteoclasts in the rat OVX model.

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Acknowledgments

We thank Suvi Suutari and Salla Ylönen for their skillful technical assistance and the Finnish Funding Agency for Technology and Innovations (TEKES) for financial support.

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Authors and Affiliations

  1. Pharmatest Services Ltd., Itäinen Pitkäkatu 4 C, Turku, 20520, Finland

    Jukka P. Rissanen, Mari I. Suominen, Zhiqi Peng & Jussi M. Halleen

Authors
  1. Jukka P. Rissanen
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  2. Mari I. Suominen
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  3. Zhiqi Peng
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  4. Jussi M. Halleen
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Corresponding author

Correspondence to Jukka P. Rissanen.

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Disclosure statement: Jukka Rissanen, Mari Suominen, and Zhiqi Peng have nothing to disclose; Jussi Halleen receives royalties from and works as a consultant of SBA Sciences, a company owned by IDS Ltd.

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Rissanen, J.P., Suominen, M.I., Peng, Z. et al. Secreted Tartrate-Resistant Acid Phosphatase 5b is a Marker of Osteoclast Number in Human Osteoclast Cultures and the Rat Ovariectomy Model. Calcif Tissue Int 82, 108–115 (2008). https://doi.org/10.1007/s00223-007-9091-4

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  • DOI: https://doi.org/10.1007/s00223-007-9091-4

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