在类风湿性关节炎中，RANKL抑制是否兼具抗吸收和促合成代谢作用？
Is RANKL inhibition both anti-resorptive and anabolic in rheumatoid arthritis?
作者信息
Sims Natalie A, Romas Evange
机构信息
St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, VIC, 3065, Australia.
Department of Medicine at St. Vincent's Hospital Melbourne, The University of Melbourne, 41 Victoria Pde, Fitzroy, VIC, 3065, Australia.
出版信息
Arthritis Res Ther. 2015 Nov 17;17:328. doi: 10.1186/s13075-015-0861-5.
Abstract
A small peptide, OP3-4, blocks receptor activator of NF-κB from binding to its ligand, receptor activator of NF-κB ligand (RANKL), and was reported recently to inhibit bone resorption, promote bone formation and protect cartilage in a preclinical rheumatoid arthritis model. The latter effects may result from inhibition of RANKL reverse signalling in osteoblasts and chondrocytes. Whether other RANKL inhibitors, such as denosumab, share this action is not known, but OP3-4 at least has potential to provide anabolic treatment for both systemic and focal bone loss in inflammatory arthritis.
摘要
一种小肽OP3 - 4可阻止核因子κB受体激活剂与其配体核因子κB受体激活剂配体（RANKL）结合，最近有报道称，在临床前类风湿性关节炎模型中，它可抑制骨吸收、促进骨形成并保护软骨。后一种作用可能是由于抑制了成骨细胞和软骨细胞中的RANKL反向信号传导。目前尚不清楚其他RANKL抑制剂（如地诺单抗）是否具有这种作用，但OP3 - 4至少有潜力为炎症性关节炎的全身性和局部性骨质流失提供合成代谢治疗。
相似文献
1
Is RANKL inhibition both anti-resorptive and anabolic in rheumatoid arthritis?在类风湿性关节炎中，RANKL抑制是否兼具抗吸收和促合成代谢作用？
Arthritis Res Ther. 2015 Nov 17;17:328. doi: 10.1186/s13075-015-0861-5.
2
The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study.一种RANKL结合肽对胶原诱导性关节炎小鼠模型关节及关节周围骨质流失的抑制作用：一项骨组织形态计量学研究
Arthritis Res Ther. 2015 Sep 12;17(1):251. doi: 10.1186/s13075-015-0753-8.
3
Unexpected Bone Formation Produced by RANKL Blockade.骨保护素抑制剂导致的意外骨形成。
Trends Endocrinol Metab. 2017 Oct;28(10):695-704. doi: 10.1016/j.tem.2017.06.003. Epub 2017 Jul 19.
4
RANKL targeted peptides inhibit osteoclastogenesis and attenuate adjuvant induced arthritis by inhibiting NF-κB activation and down regulating inflammatory cytokines.RANKL 靶向肽通过抑制 NF-κB 激活和下调炎症细胞因子抑制破骨细胞生成并减轻佐剂诱导的关节炎。
Chem Biol Interact. 2013 Apr 25;203(2):467-79. doi: 10.1016/j.cbi.2012.12.016. Epub 2013 Jan 17.
5
Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis.地诺单抗：靶向RANKL通路治疗类风湿关节炎。
Expert Opin Biol Ther. 2017 Jan;17(1):119-128. doi: 10.1080/14712598.2017.1263614. Epub 2016 Nov 30.
6
Clinical applications of RANK-ligand inhibition.RANK 配体抑制的临床应用。
Intern Med J. 2009 Feb;39(2):110-6. doi: 10.1111/j.1445-5994.2008.01732.x.
7
RANKL: A therapeutic target for bone destruction in rheumatoid arthritis.核因子κB受体活化因子配体：类风湿关节炎骨破坏的治疗靶点。
Mod Rheumatol. 2018 Jan;28(1):9-16. doi: 10.1080/14397595.2017.1369491. Epub 2017 Sep 18.
8
Anti-receptor activator of nuclear factor κB ligand antibody treatment increases osteoclastogenesis-promoting IL-8 in patients with rheumatoid arthritis.抗核因子 κB 配体受体抗体治疗可增加类风湿关节炎患者促进破骨细胞形成的白细胞介素-8。
Int Immunol. 2019 Apr 26;31(5):277-285. doi: 10.1093/intimm/dxz009.
9
[Anti-RANKL antibody].[抗RANKL抗体]
Nihon Rinsho. 2015 Oct;73(10):1690-5.
10
Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL.地诺单抗是一种针对核因子κB受体活化因子配体（RANKL）的全人单克隆抗体，在表达嵌合型（鼠/人）RANKL的基因敲入小鼠中，它可抑制骨吸收并增加骨密度。
J Bone Miner Res. 2009 Feb;24(2):182-95. doi: 10.1359/jbmr.081112.
引用本文的文献
1
Personalized Therapeutic Strategies in the Management of Osteoporosis in Patients with Autoantibody-Positive Rheumatoid Arthritis.自身抗体阳性类风湿关节炎患者骨质疏松症管理中的个性化治疗策略
J Clin Med. 2022 Apr 22;11(9):2341. doi: 10.3390/jcm11092341.
2
The role of osteoblasts in bone metastasis.成骨细胞在骨转移中的作用。
J Bone Oncol. 2016 Apr 13;5(3):124-127. doi: 10.1016/j.jbo.2016.03.007. eCollection 2016 Sep.
3
Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.肽类药物通过mTORC1信号通路加速BMP - 2诱导的颅骨再生并刺激成骨细胞分化。
Bioessays. 2016 Aug;38(8):717-25. doi: 10.1002/bies.201600104. Epub 2016 Jun 27.
本文引用的文献
1
The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study.一种RANKL结合肽对胶原诱导性关节炎小鼠模型关节及关节周围骨质流失的抑制作用：一项骨组织形态计量学研究
Arthritis Res Ther. 2015 Sep 12;17(1):251. doi: 10.1186/s13075-015-0753-8.
2
Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone.破骨细胞中的糖蛋白130（Gp130）/白细胞介素-6（IL-6）信号传导促进骨膜和小梁骨中的骨形成。
Bone. 2015 Dec;81:343-351. doi: 10.1016/j.bone.2015.08.005. Epub 2015 Aug 7.
3
Risk of hospitalized infection among rheumatoid arthritis patients concurrently treated with a biologic agent and denosumab.类风湿关节炎患者同时使用生物制剂和地舒单抗治疗后的住院感染风险。
Arthritis Rheumatol. 2015 Jun;67(6):1456-64. doi: 10.1002/art.39075.
4
Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab.成年食蟹猴基于模型的持续骨形成可能有助于地诺单抗治疗下骨密度的持续增加。
J Bone Miner Res. 2015 Jul;30(7):1280-9. doi: 10.1002/jbmr.2480.
5
Implications of osteoblast-osteoclast interactions in the management of osteoporosis by antiresorptive agents denosumab and odanacatib.抗吸收剂地舒单抗和odanacatib 治疗骨质疏松症中成骨细胞-破骨细胞相互作用的意义。
Curr Osteoporos Rep. 2014 Mar;12(1):98-106. doi: 10.1007/s11914-014-0196-1.
6
Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that possesses osteoclastogenesis inhibitory activity.一种核因子-κB 配体（RANKL）受体结合肽可刺激治疗小鼠皮质骨的骨形成，该肽具有破骨细胞生成抑制活性。
J Biol Chem. 2013 Feb 22;288(8):5562-71. doi: 10.1074/jbc.M112.426080. Epub 2013 Jan 14.
7
Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment.类风湿关节炎中的骨侵蚀：机制、诊断与治疗。
Nat Rev Rheumatol. 2012 Nov;8(11):656-64. doi: 10.1038/nrrheum.2012.153. Epub 2012 Sep 25.
8
Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies.地舒单抗对骨组织形态计量学的影响：FREEDOM 和 STAND 研究。
J Bone Miner Res. 2010 Oct;25(10):2256-65. doi: 10.1002/jbmr.149.
9
Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial.地诺单抗对类风湿关节炎结构损伤、骨密度和骨转换的治疗效果：一项为期十二个月的多中心、随机、双盲、安慰剂对照的II期临床试验。
Arthritis Rheum. 2008 May;58(5):1299-309. doi: 10.1002/art.23417.
10
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.每年一次唑来膦酸用于治疗绝经后骨质疏松症。
N Engl J Med. 2007 May 3;356(18):1809-22. doi: 10.1056/NEJMoa067312.
Zotero 插件