重组RANKL（Receptor Activator of Nuclear Factor-κB Ligand，AbMole，M11464）是一种在骨代谢和免疫调控中发挥重要作用的细胞因子。在分子机理上，RANKL通过结合其受体RANK激活下游信号通路（如NF-κB、MAPK、Akt/mTOR等），并调控细胞分化、增殖和炎症反应[1]。例如，RANKL（TNFSF11）在RAW 264.7小鼠巨噬细胞系中，以浓度依赖性方式诱导破骨细胞分化[2]。

此外，RANKL（重组RANKL蛋白）还能通过抑制MDM2和Ki-67表达，降低人肥大细胞系HMC-1的增殖能力，并诱导细胞衰老[3]。重组RANKL（rRANKL）在人椎间盘细胞（IVD cells）中，与重组骨保护素（rhOPG，Osteoprotegerin）联用，可调节基质金属蛋白酶（MMP-3/MMP-13）和IL-1β（白介素1β）的表达[4]。RANKL可与BMP-2（重组BMP-2蛋白）协同调控成骨-破骨平衡，在小鼠成骨细胞系MC3T3-E1和破骨前体细胞系RAW264.7的研究中证实了这一点[5]。此外，IL-19（白介素19）可通过抑制RANKL诱导的NF-κB和p38MAPK活化，阻断RAW264.7细胞的破骨分化[6]。

动物实验进一步揭示了重组RANKL的生物学功能：在脓毒症相关急性肾损伤（SA-AKI）模型中，重组RANKL的注射降低了炎症因子IL-1β、TNF-α 水平并减轻肾组织损伤[7]。AbMole为全球科研客户提供高纯度、高生物活性的抑制剂、细胞因子、人源单抗、天然产物、荧光染料、多肽、化合物库、抗生素等科研试剂，全球大量文献专利引用。

参考文献及鸣谢

[1] Yeom, J.; Ma, S.; Yim, D. J.; et al. Surface proteins of Propionibacterium freudenreichii MJ2 inhibit RANKL-induced osteoclast differentiation by lipocalin-2 upregulation and lipocalin-2-mediated NFATc1 inhibition. Scientific reports 2023, 13 (1), 15644.

[2] Ding, M.; Chen, Z.; Cho, E.; et al. Crucial Role of Lysine-Specific Histone Demethylase 1 in RANKL-Mediated Osteoclast Differentiation. International journal of molecular sciences 2023, 24 (4).

[3] Lim, J. H.; Kim, H. Y.; Kang, H. G.; et al. RANKL down-regulates the mast cell proliferation through inducing senescence. Cytokine 2022, 159, 156018.

[4] Sano, T.; Akeda, K.; Yamada, J.; et al. Expression of the RANK/RANKL/OPG system in the human intervertebral disc: implication for the pathogenesis of intervertebral disc degeneration. BMC musculoskeletal disorders 2019, 20 (1), 225.

[5] Li, J.; Sakisaka, Y.; Nemoto, E.; et al. Cementocyte-derived extracellular vesicles regulate osteoclastogenesis and osteoblastogenesis. Journal of dental sciences 2024, 19 (4), 2236-2246.

[6] Tsubaki, M.; Takeda, T.; Matsuda, T.; et al. Interleukin 19 suppresses RANKL-induced osteoclastogenesis via the inhibition of NF-kappaB and p38MAPK activation and c-Fos expression in RAW264.7 cells. Cytokine 2021, 144, 155591.

[7] Niu, X.; Wang, C.; Li, H.; et al. Role of OPG/RANKL/RANK/TLR4 signaling pathway in sepsis-associated acute kidney injury. BMC nephrology 2024, 25 (1), 205.