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CLL cells affect osteoblastogenesis/osteoclastogenesis
compensate for the lack of soluble RANKL. Incrementation of the number of seeded monocytes (from 1.3x105/well to 2.6x105/well), cultured with MCSF+CLL-cm, also failed to give rise to mature osteo- clasts that were fully competent at matrix erosion. The ability to erode bone does, therefore, appear to be strictly
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related to the presence of large, fully differentiated osteo- clasts, characterized by a typical sealing zone. Nurse-like cells, tumor-associated macrophages typically found in the CLL microenvironment,11,26 although TRAP+, were also devoid of bone surface resorbing activity (Figure 5D).
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Figure 5. The addition of CLL-conditioned media enhances the resorption activity of MCSF+RANKL-derived osteoclasts. (A) Osteoclasts derived in the presence of CLL- conditioned media (cm) showed a significant enhancement in bone resorption activity in comparison with controls derived with only MCSF+RANKL. Images are repre- sentative of two different experiments with CLL-cm derived from three CLL patients. (B) On the other hand, osteoclasts derived in the presence of MCSF+CLL-cm, without RANKL pre-activation, created a few pits of resorption. Nurse-like cells (NLC), although TRAP+, did not resorb bone. Images are representative of two experiments. (C) The addition of CLL-cm to MCSF-RANKL pre-stimulated monocytes significantly increased the ability of osteoclasts to resorb bone; n: number of visual fields assessed in two different experiments and CLL-cm derived from three CLL patients. (D) Increasing the number of seeded monocytes (1.3x105 or 2.6x105/well) stimulated with MCSF only did not result in enhanced resorption activity. Increasing the number of CLL cells (1x106 or 2x106/well) expressing RANKL on their surface was also not suf- ficient to compensate for the lack of soluble RANKL. NLC did not display bone resorbing activity n: number of visual fields assessed in two experiments.
haematologica | 2021; 106(10)
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