重組RANKL的生物學(xué)功能及在骨代謝和免疫調(diào)節(jié)中的應(yīng)用

重組RANKL（Receptor Activator of Nuclear Factor-κB Ligand，AbMole，M11464）是一種在骨代謝和免疫調(diào)控中發(fā)揮重要作用的細(xì)胞因子。在分子機(jī)理上，RANKL通過結(jié)合其受體RANK激活下游信號通路（如NF-κB、MAPK、Akt/mTOR等），并調(diào)控細(xì)胞分化、增殖和炎癥反應(yīng)[1]。例如，RANKL（TNFSF11）在RAW 264.7小鼠巨噬細(xì)胞系中，以濃度依賴性方式誘導(dǎo)破骨細(xì)胞分化[2]。此外，重組RANKL（Receptor Activator of Nuclear Factor-κB Ligand，AbMole，M11464）還能通過抑制MDM2和Ki-67表達(dá)，降低人肥大細(xì)胞系HMC-1的增殖能力，并誘導(dǎo)細(xì)胞衰老[3]。重組重組RANKL（Receptor Activator of Nuclear Factor-κB Ligand，AbMole，M11464）在人椎間盤細(xì)胞（IVD cells）中，與重組骨保護(hù)素（rhOPG，Osteoprotegerin）聯(lián)用，可調(diào)節(jié)基質(zhì)金屬蛋白酶（MMP-3/MMP-13）和IL-1β（白介素1β）的表達(dá)[4]。RANKL可與BMP-2（重組BMP-2蛋白）協(xié)同調(diào)控成骨-破骨平衡，在小鼠成骨細(xì)胞系MC3T3-E1和破骨前體細(xì)胞系RAW264.7的研究中證實(shí)了這一點(diǎn)[5]。此外，IL-19（白介素19）可通過抑制RANKL誘導(dǎo)的NF-κB和p38MAPK活化，阻斷RAW264.7細(xì)胞的破骨分化[6]。動物實(shí)驗(yàn)進(jìn)一步揭示了重組RANKL的生物學(xué)功能：在膿毒癥相關(guān)急性腎損傷（SA-AKI）模型中，重組RANKL的注射降低了炎癥因子IL-1β、TNF-α  水平并減輕腎組織損傷[7]。AbMole為全球科研客戶提供高純度、高生物活性的抑制劑、細(xì)胞因子、人源單抗、天然產(chǎn)物、熒光染料、多肽、靶點(diǎn)蛋白、化合物庫、抗生素等科研試劑，全球大量文獻(xiàn)專利引用。
 
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參考文獻(xiàn)及鳴謝
[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.