Delgado-Calle Jesus, Bellido Teresita, Roodman G David
aDepartment of Anatomy and Cell Biology bDivision of Endocrinology, Department of Medicine cDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine dRoudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
Curr Opin Support Palliat Care. 2014 Dec;8(4):407-13. doi: 10.1097/SPC.0000000000000090.
Despite the increased knowledge of osteocyte biology, the contribution of this most abundant bone cell to the development and progression of multiple myeloma in bone is practically unexplored.
Multiple myeloma bone disease is characterized by exacerbated bone resorption and the presence of osteolytic lesions that do not heal because of a concomitant reduction in bone formation. Osteocytes produce molecules that regulate both bone formation and resorption. Recent findings suggest that the life span of osteocytes is compromised in multiple myeloma patients with bone lesions. In addition, multiple myeloma cells affect the transcriptional profile of osteocytes by upregulating the production of pro-osteoclastogenic cytokines, stimulating osteoclast formation and activity. Further, patients with active multiple myeloma have elevated circulating levels of sclerostin, a potent inhibitor of bone formation which is specifically expressed by osteocytes in bone.
Understanding the contribution of osteocytes to the mechanisms underlying the skeletal consequences of multiple myeloma bone disease has the potential to provide important new therapeutic strategies that specifically target multiple myeloma-osteocyte interactions.
尽管对骨细胞生物学的认识有所增加，但这种最丰富的骨细胞对骨中多发性骨髓瘤的发生和发展的作用实际上尚未得到探索。
多发性骨髓瘤骨病的特征是骨吸收加剧，且存在由于骨形成同时减少而无法愈合的溶骨性病变。骨细胞产生调节骨形成和吸收的分子。最近的发现表明，在患有骨病变的多发性骨髓瘤患者中，骨细胞的寿命受到损害。此外，多发性骨髓瘤细胞通过上调促破骨细胞生成细胞因子的产生来影响骨细胞的转录谱，刺激破骨细胞的形成和活性。此外，活动性多发性骨髓瘤患者循环中硬化蛋白水平升高，硬化蛋白是一种由骨中的骨细胞特异性表达的强效骨形成抑制剂。
了解骨细胞对多发性骨髓瘤骨病骨骼后果潜在机制的作用，有可能提供针对多发性骨髓瘤-骨细胞相互作用的重要新治疗策略。
