Department of Haematology, No. 2 Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Arch Med Sci. 2010 Aug 30;6(4):496-504. doi: 10.5114/aoms.2010.14459. Epub 2010 Sep 7.
Myeloma bone disease (MBD) is the result of the increased activity of osteoclasts (OCs), which is not accompanied by a comparable increase of osteoblast (OB) function, thus leading to enhanced bone resorption. Osteoblasts can also regulate osteoclast activity through expression of cytokines, such as receptor activator of nuclear factor-κB ligand (RANKL), which activates osteoclast differentiation, and osteoprotegerin (OPG), which inhibits RANKL by acting as a decoy receptor.
Based on a series of 21 patients with multiple myeloma (MM) and human osteoblast cell line HFOB1.19, we provide evidence that the bone marrow-derived mesenchymal stem cells (BMMSCs) of patients with MM exhibit normal phenotype, but showed reduced efficiency to differentiate into OBs as compared with normal controls.
In vitro assays showed that MM cells inhibited the potential of osteogenic differentiation of BMMSCs from healthy controls and rendered the OBs sensitive to TRAIL-induced apoptosis. There was no evidence of the formation of tartrate-resistant acid phosphatase positive OCs. The osteogenic differentiation of HFOB1.19 was also inhibited in the presence of RPMI 8266 or XG7 MM cells, as confirmed by von Kossa and ALP staining. Osteoblast s induced from BMMSCs supported survival and proliferation of MM cells, especially when the MM cells were cultured in medium containing rhTRAIL and dexamethasone. Multiple myeloma cells proliferated and grew well in the presence of residual OBs.
Besides OCs, our results demonstrated that OBs and MM cells were dependent upon each other and made a microenvironment suitable for MM cells.
骨髓瘤骨病（MBD）是破骨细胞（OCs）活性增加的结果，这种增加并不伴有成骨细胞（OB）功能的相应增加，从而导致骨吸收增强。成骨细胞还可以通过表达细胞因子来调节破骨细胞的活性，例如核因子-κB 受体激活剂配体（RANKL），它激活破骨细胞分化，以及骨保护素（OPG），它通过充当诱饵受体来抑制 RANKL。
基于 21 例多发性骨髓瘤（MM）患者和人成骨细胞系 HFOB1.19，我们提供了证据表明，MM 患者的骨髓间充质干细胞（BMMSCs）表现出正常的表型，但与正常对照相比，向 OB 分化的效率降低。
体外实验表明，MM 细胞抑制了健康对照者 BMMSCs 的成骨分化潜能，并使 OB 对 TRAIL 诱导的凋亡敏感。没有证据表明形成抗酒石酸酸性磷酸酶阳性破骨细胞。在 RPMI 8266 或 XG7 MM 细胞存在的情况下，HFOB1.19 的成骨分化也受到抑制，这通过 von Kossa 和 ALP 染色得到证实。从 BMMSCs 诱导的成骨细胞支持 MM 细胞的存活和增殖，特别是当 MM 细胞在含有 rhTRAIL 和地塞米松的培养基中培养时。在残留 OBs 的存在下，MM 细胞增殖和生长良好。
除了 OCs，我们的结果还表明 OBs 和 MM 细胞相互依赖，并形成了一个适合 MM 细胞的微环境。
