Department of Orthopaedics and Rehabilitation, Vanderbilt University, Nashville, TN, 37232, USA.
Bone. 2011 Jan;48(1):44-53. doi: 10.1016/j.bone.2010.06.007. Epub 2010 Jun 16.
Bone remodeling is a delicate balancing act between the bone matrix synthesizing osteoblasts and bone resorbing osteoclasts. Active bone metastases typically subvert this process to generate lesions that are comprised of extensive areas of pathological osteogenesis and osteolysis. The resultant increase in bone matrix remodeling enhances cytokine/growth factor bioavailability thus creating a vicious cycle that stimulates tumor progression. Given the extent of matrix remodeling occurring in the tumor-bone microenvironment, the expression of matrix metalloproteinases (MMPs) would be expected, since collectively they have the ability to degrade all components of the extracellular matrix (ECM). However, in addition to being "matrix bulldozers", MMPs control the bioavailability and bioactivity of factors such as RANKL and TGFβ that have been described as crucial for tumor-bone interaction, thus implicating MMPs as key regulators of the vicious cycle of bone metastases.
骨重建是骨基质合成的成骨细胞和骨吸收的破骨细胞之间的微妙平衡。活跃的骨转移通常会破坏这个过程，生成由广泛的病理性成骨和骨溶解组成的病变。骨基质重塑的增加增加了细胞因子/生长因子的生物利用度，从而形成一个刺激肿瘤进展的恶性循环。鉴于肿瘤骨微环境中发生的基质重塑的程度，可以预期基质金属蛋白酶 (MMPs) 的表达，因为它们共同具有降解细胞外基质 (ECM) 的所有成分的能力。然而，除了作为“基质推土机”之外，MMPs 还控制着 RANKL 和 TGFβ 等因子的生物利用度和生物活性，这些因子被描述为肿瘤骨相互作用所必需的，因此 MMPs 是骨转移恶性循环的关键调节剂。
