Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth

Jesus Delgado-Calle, J. Anderson, M. D. Cregor, K. W. Condon, S. A. Kuhstoss, Lilian Plotkin, Teresita Bellido, G. David Roodman

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl), an osteocyte-derived inhibitor of Wnt/β-catenin signaling, is elevated in MM patient sera and increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM. Sost/Scl inhibition increased osteoblast numbers, stimulated new bone formation and decreased osteoclast number in MM-colonized bone. Further, Sost/Scl inhibition did not affect tumor growth in vivo or anti-myeloma drug efficacy in vitro. These results identify the osteocyte as a major contributor to the deleterious effects of MM in bone and osteocyte-derived Scl as a promising target for the treatment of established MM-induced bone disease. Further, Scl did not interfere with efficacy of chemotherapy for MM, suggesting that combined treatment with anti-myeloma drugs and Scl-Ab should effectively control MM growth and bone disease, providing new avenues to effectively control MM and bone disease in patients with active MM.

Original languageEnglish (US)
Pages (from-to)2686-2694
Number of pages9
JournalLeukemia
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2017

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Bone Diseases
Multiple Myeloma
Pharmacology
Growth
Neoplasms
Osteocytes
Bone and Bones
Osteogenesis
Catenins
Osteolysis
Gene Deletion
Osteoclasts
Bone Resorption
Osteoblasts
Pharmaceutical Preparations
Anti-Idiotypic Antibodies

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth. / Delgado-Calle, Jesus; Anderson, J.; Cregor, M. D.; Condon, K. W.; Kuhstoss, S. A.; Plotkin, Lilian; Bellido, Teresita; Roodman, G. David.

In: Leukemia, Vol. 31, No. 12, 01.12.2017, p. 2686-2694.

Research output: Contribution to journalArticle

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