Myeloma impairs mature osteoblast function but causes early expansion of osteo-progenitors: temporal changes in bone physiology and gene expression in the KMS12BM model

British Journal of Haematology
Deepika KassenKwee L Yong

Abstract

Myeloma bone disease results from an uncoupling of osteoclastic resorption and osteoblastic bone formation, but early changes in osteogenic function remain poorly defined. We used the KMS12BM xenograft model to investigate cellular and molecular events at early and late stages of disease. Lytic lesions and changes in osteoblast and osteoclast numbers occur late (8 weeks), however, micro-computed tomography of femora revealed significant reduction in bone volume at earlier disease stages (3 weeks) when tumour burden is low. Calcein labelling demonstrated reduced mineralization and bone formation at 3 weeks, suggesting functional impairment despite preserved osteoblast numbers. Osteo-progenitors from compact bone increased early (1 week), but fell at 3 weeks and were profoundly suppressed by 8 weeks. Exposure of osteoblast progenitors to multiple myeloma (MM) cells in vitro induced cell cycling, suggesting a mechanistic basis for early expansion of osteo-progenitors. We observed temporal changes in chemokine, osteogenic and osteoclastogenic genes in the stromal compartment. Notably, an early rise in CCL3 may underlie functional changes in mature osteoblasts at 3 weeks. Our data indicate that MM has distinct effects on mature oste...Continue Reading

References

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Citations

Aug 9, 2016·Progress in Biophysics and Molecular Biology·Hao XiLu Gao
Mar 1, 2017·Current Hematologic Malignancy Reports·Nicholas BinghamAndrew Spencer
Oct 26, 2018·Pharmaceutics·Sonia ValletKlaus Podar
Dec 2, 2020·Stem Cell Research & Therapy·Dan ZhangJinsong Hu
Dec 8, 2020·Molecular Carcinogenesis·Piotr ŁacinaKatarzyna Bogunia-Kubik
Aug 11, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Noopur S RajeEvangelos Terpos

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