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Published on: May 10, 2017
Sclerostin is overexpressed by plasma cells from multiple myeloma patients
Giacomina Brunetti1, Angela Oranger, Giorgio Mori
1Department of Basic Medical Science, Section of Human Anatomy and Histology, University of Bari, Bari, Italy. g.brunetti@biotec.uniba.it
Abstract:
Sclerostin, an osteocyte-expressed negative regulator of bone formation, is one of the inhibitors of Wnt signaling that is a critical pathway in the correct process of osteoblast differentiation. It has been demonstrated that Wnt signaling through the secretion of Wnt inhibitors, such as DKK1, sFRP-2, and sFRP-3, plays a key role in the decreased osteoblast activity associated with multiple myeloma (MM) bone disease. We provide evidence that sclerostin is expressed by myeloma cells that are human myeloma cell lines and plasma cells (CD138(+) cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. Moreover, we show that there are no differences in sclerostin serum levels between MM patients and controls. Thus, our data indicate that MM cells, as a sclerostin source in the BM, could create a microenvironment with high sclerostin concentration that could contribute toward inhibiting osteoblast differentiation.
Insights
Multiple myeloma cells, not serum, express sclerostin, a Wnt signaling inhibitor. This finding suggests myeloma cells create a local bone marrow environment that hinders osteoblast differentiation and bone formation in patients.
Area of Science:
- Bone biology
- Oncology
- Endocrinology
Background:
- Sclerostin is an osteocyte-expressed inhibitor of Wnt signaling, crucial for osteoblast differentiation.
- Wnt signaling inhibitors like DKK1, sFRP-2, and sFRP-3 are implicated in multiple myeloma (MM) bone disease.
- The role of sclerostin specifically in MM bone disease requires further elucidation.
Purpose of the Study:
- To investigate the source of sclerostin in the bone marrow of multiple myeloma patients.
- To determine if myeloma cells themselves express sclerostin.
- To assess the relationship between serum sclerostin levels and MM bone disease.
Main Methods:
- Analysis of sclerostin expression in human myeloma cell lines.
- Immunohistochemical analysis of plasma cells (CD138(+) cells) from bone marrow of MM patients.
- Measurement of serum sclerostin levels in MM patients and healthy controls.
Main Results:
- Sclerostin is expressed by myeloma cells and plasma cells from MM patients.
- No significant difference in serum sclerostin levels was observed between MM patients and controls.
- Myeloma cells are identified as a potential source of sclerostin within the bone marrow microenvironment.
Conclusions:
- Multiple myeloma cells, rather than serum, are a significant source of sclerostin in the bone marrow.
- High local concentrations of sclerostin produced by myeloma cells may inhibit osteoblast differentiation.
- This localized sclerostin production by myeloma cells could contribute to the pathogenesis of MM bone disease.