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Serum from Postmenopausal Women Directs Differentiation of Human Clonal Osteoprogenitor Cells from an Osteoblastic toward an Adipocytic Phenotype

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Abstract

A consistent observation in osteoporosis is bone volume reduction accompanied by increased marrow adipose tissue. No single cause linking the two phenomena has yet been identified. In a human progenitor cell clone (hOP 7) derived from bone marrow, however, we have demonstrated that rabbit serum can direct differentiation away from an osteoblast lineage to one of adipocytes. We now report on whether human serum has a similar effect. Serum was collected from 10 pre- and 10 postmenopausal women and from the 10 postmenopausal women before and following 6-week hormone replacement therapy (HRT). hOP 7 cells were cultured with the various sera, and after 7-14 days adipocytogenesis was determined by oil red O staining and lipoprotein lipase (LPL) and glycerol 3-phosphate dehydrogenase (G3PDH) expression. Incubation with 10% premenopausal serum led to labeling of 10.9% of cells (P < 0.05) with oil red O, whereas application of 10% postmenopausal serum led to a much larger effect, 43.5% labeling (P < 0.001 with respect to premenopausal serum). Oil red O positivity was accompanied by loss of type I collagen expression and increased LPL and G3PDH expression. HRT did not reverse the adipocytogenic effect of postmenopausal serum. In conclusion, serum from postmenopausal women contains factors that steer hOP 7 bone progenitor cells toward an adipocytic phenotype, irrespective of HRT. The study suggests a role for serum factors in the development of fatty marrow in postmenopausal osteoporosis.

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Acknowledgment

We are grateful to the Arthritis Research Campaign, the Nuffield Foundation, the University of Sheffield, and Cardiff University for supporting this work.

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Authors and Affiliations

  1. Department of Oral Surgery, Medicine and Pathology, Dental School, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK

    Bradley Stringer & Alastair Sloan

  2. Department of Dental Health and Biological Sciences, Dental School, Cardiff University, Cardiff, CF14 4XY, UK

    Rachel Waddington

  3. Health Care Research Center, Proctor and Gamble, Box 1057, Mason, OH, 45040-9462, USA

    Adam Houghton

  4. Llandough Hospital, Medical School, Cardiff University, Cardiff, CF64 2XX, UK

    Mike Stone

  5. Nuffield Department of Orthopedic Surgery, University of Oxford, Willmill Rd. Headington, Oxford, OX37LD, UK

    Graham Russell

  6. School of Biosciences, Cardiff University, P.O.Box 911, Cardiff, CF10 3US, UK

    George Foster

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  1. Bradley Stringer
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Correspondence to Bradley Stringer.

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Stringer, B., Waddington, R., Sloan, A. et al. Serum from Postmenopausal Women Directs Differentiation of Human Clonal Osteoprogenitor Cells from an Osteoblastic toward an Adipocytic Phenotype. Calcif Tissue Int 80, 233–243 (2007). https://doi.org/10.1007/s00223-007-9016-2

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