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The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice

Study · animal · International journal of molecular sciences · 2021 · DOI 10.3390/ijms23010055 · PMID 35008482

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

In this mouse study, researchers examined Cibinetide (CIB), a non-erythropoietic EPO analogue that binds the heteromeric EPO receptor-CD131 complex, for its role in bone metabolism, given alone or combined with erythropoietin (EPO). One month of CIB treatment increased cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Administering CIB for five consecutive days alongside EPO on days one and four reduced the number of osteoclast progenitors (Lin-CD11b-Ly6Chi CD115+) by 42.8% compared to EPO alone. CIB alone or combined with EPO also inhibited osteoclastogenesis in vitro. The authors describe CIB, alone or with EPO, as a candidate for further study of bone loss associated with EPO treatment.

Abstract

The two erythropoietin (EPO) receptor forms mediate different cellular responses to erythropoietin. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. In the skeletal system, EPO stimulates osteoclast precursors and induces bone loss. However, the underlying molecular mechanisms are still elusive. Here, we evaluated the role of the heteromeric complex in bone metabolism in vivo and in vitro by using Cibinetide (CIB), a non-erythropoietic EPO analogue that exclusively binds the heteromeric receptor. CIB is administered either alone or in combination with EPO. One month of CIB treatment significantly increased the cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Similarly, administration of CIB for five consecutive days to female mice that concurrently received EPO on days one and four, reduced the number of osteoclast progenitors, defined by flow cytometry as Lin-CD11b-Ly6Chi CD115+, by 42.8% compared to treatment with EPO alone. In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment.

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