内源性大麻素系统用于骨质疏松症预防与治疗的研究进展

doi:10.11958/20230510

天津医药 ›› 2023, Vol. 51 ›› Issue (9): 1020-1024.doi: 10.11958/20230510

• 综述 • 上一篇

内源性大麻素系统用于骨质疏松症预防与治疗的研究进展

王蕾¹(), 杨涛¹, 耿立成¹, 孙天威²^,^△()

1.天津市人民医院麻醉科（邮编300121）
2.天津市人民医院脊柱外科（邮编300121）

收稿日期:2023-04-17 修回日期:2023-05-21 出版日期:2023-09-15 发布日期:2023-09-13
通讯作者: △E-mail：tumcmzk@163.com
作者简介:王蕾（1972），男，主治医师，主要从事麻醉药理与骨质疏松症疼痛机制研究。E-mail：1817978005@qq.com
基金资助:
天津市科技计划项目(22JCZDJC00250)

Research progress of endocannabinoid system for prevention and treatment of osteoporosis

WANG Lei¹(), YANG Tao¹, GENG Licheng¹, SUN Tianwei²^,^△()

1. Department of Anesthesiology, Tianjin Union Medical Center, Tianjin 300121, China
2. Department of Spine Surgery, Tianjin Union Medical Center, Tianjin 300121, China

Received:2023-04-17 Revised:2023-05-21 Published:2023-09-15 Online:2023-09-13
Contact: △E-mail：tumcmzk@163.com

王蕾, 杨涛, 耿立成, 孙天威. 内源性大麻素系统用于骨质疏松症预防与治疗的研究进展[J]. 天津医药, 2023, 51(9): 1020-1024.

WANG Lei, YANG Tao, GENG Licheng, SUN Tianwei. Research progress of endocannabinoid system for prevention and treatment of osteoporosis[J]. Tianjin Medical Journal, 2023, 51(9): 1020-1024.

摘要/Abstract

摘要：

骨质疏松症（OP）是一种以骨量减少和骨组织微结构改变为特征的全身性骨骼疾病，其发病率呈逐年上升趋势，已经成为严重的公共健康隐患。成骨细胞和破骨细胞介导的骨代谢失衡是OP的重要发病机制。内源性大麻素系统（ECS）广泛分布于骨组织中，参与调节成骨细胞及破骨细胞的多种生物学功能，可能是OP的潜在治疗靶点，靶向ECS进行深入研究能够为OP的临床治疗提供新的理论依据。就ECS在调控OP发病过程中的具体作用进行了综述。

关键词: 骨质疏松, 受体, 大麻酚, 大麻素受体调节剂, 成骨细胞, 骨代谢

Abstract:

Osteoporosis (OP) is a kind of systemic bone disease characterized by reduced bone mass and changes of bone microstructure. The incidence rate of OP has been increasing gradually year by year, which has become a severe public health issue. The imbalance of bone metabolism mediated by osteoblasts and osteoclast is an important pathogenesis of OP. The endocannabinoid system (ECS) is widely distributed in bone tissue and participates in regulating multiple biological effects of osteoblasts and osteoclasts, suggesting that ECS may be a potential treatment target of OP. Further study on targeting ESC can provide a new theoretical basis for the clinical treatment of OP. This article reviews the specific role of ECS in regulating the pathogenesis of OP.

Key words: osteoporosis, receptors, cannabinoid, cannabinoid receptor modulators, osteoblasts, bone metabolism

中图分类号:

R681.4，R614，R285

参考文献 37

[1]	JOHNSTON C B, DAGAR M. Osteoporosis in older adults[J]. Med Clin North Am, 2020, 104(5):873-884. doi:10.1016/j.mcna.2020.06.004.
[2]	罗丽梅, 李杰, 杨帆, 等. 骨质疏松发病机制及治疗药物研究进展[J]. 中国骨质疏松杂志, 2020, 26(4):610-614.
	LUO L M, LI J, YANG F, et al. Research progress of mechanism and drug treatment of osteoporosis[J]. Chin J Osteoporos, 2020, 26(4):610-614. doi:10.3969/j.issn.1006-7108.
[3]	KAUR M, NAGPAL M, SINGH M. Osteoblast-n-osteoclast:Making headway to osteoporosis treatment[J]. Curr Drug Targets, 2020, 21(16):1640-1651. doi:10.2174/1389450121666200731173522.
[4]	TUCCI M A, PRIDE Y, STRICKLAND S, et al. Delayed systemic treatment with cannabinoid receptor 2 agonist mitigates spinal cord injury-induced osteoporosis more than acute treatment directly after injury[J]. Neurotrauma Rep, 2021, 2(1):270-284. doi:10.1089/neur.2020.0059.
[5]	PAOLETTA M, MORETTI A, LIGUORI S, et al. Role of the endocannabinoid/endovanilloid system in the modulation of osteoclast activity in Paget's disease of bone[J]. Int J Mol Sci, 2021, 22(18):10158. doi:10.3390/ijms221810158.
[6]	FRAHER D, MANN R J, DUBUISSON M J, et al. The endocannabinoid system and retinoic acid signaling combine to influence bone growth[J]. Mol Cell Endocrinol, 2021, 529:111267. doi:10.1016/j.mce.2021.111267.
[7]	LEGARE C A, RAUP-KONSAVAGE W M, VRANA K E. Therapeutic potential of cannabis,cannabidiol,and cannabinoid-based pharmaceuticals[J]. Pharmacology, 2022, 107(3/4):131-149. doi:10.1159/000521683.
[8]	KEIMPEMA E, DI MARZO V, HARKANY T. Biological basis of cannabinoid medicines[J]. Science, 2021, 374(6574):1449-1450. doi:10.1126/science.abf6099.
[9]	LU H C, MACKIE K. Review of the endocannabinoid system[J]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2021, 6(6):607-615. doi:10.1016/j.bpsc.2020.07.016.
[10]	ALMOGI-HAZAN O, OR R. Cannabis,the endocannabinoid system and immunity-the journey from the bedside to the bench and back[J]. Int J Mol Sci, 2020, 21(12):4448. doi:10.3390/ijms21124448.
[11]	OSAFO N, YEBOAH O K, ANTWI A O. Endocannabinoid system and its modulation of brain,gut,joint and skin inflammation[J]. Mol Biol Rep, 2021, 48(4):3665-3680. doi:10.1007/s11033-021-06366-1.
[12]	CRISTINO L, BISOGNO T, Di MARZO V. Cannabinoids and the expanded endocannabinoid system in neurological disorders[J]. Nat Rev Neurol, 2020, 16(1):9-29. doi:10.1038/s41582-019-0284-z.
[13]	RAPHAEL-MIZRAHI B, GABET Y. The cannabinoids effect on bone formation and bone healing[J]. Curr Osteoporos Rep, 2020, 18(5):433-438. doi:10.1007/s11914-020-00607-1.
[14]	XIN Y, TANG A, PAN S, et al. Components of the endocannabinoid system and effects of cannabinoids against bone diseases: a mini-review[J]. Front Pharmacol, 2021, 12:793750. doi:10.3389/fphar.2021.793750.
[15]	TAM J, OFEK O, FRIDE E, et al. Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling[J]. Mol Pharmacol, 2006, 70(3):786-792. doi:10.1124/mol.106.026435.
[16]	IDRIS A I, SOPHOCLEOUS A, LANDAO-BASSONGA E, et al. Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells[J]. Cell Metab, 2009, 10(2):139-147. doi:10.1016/j.cmet.2009.07.006.
[17]	SAMIR S M, MALEK H A. Effect of cannabinoid receptors 1 modulation on osteoporosis in a rat model of different ages[J]. J Physiol Pharmacol, 2014, 65(5):687-694.
[18]	GALVE-ROPERH I, CHIURCHIU V, DIAZ-ALONSO J, et al. Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation[J]. Prog Lipid Res, 2013, 52(4):633-650. doi:10.1016/j.plipres.2013.05.004.
[19]	GASPERI V, GUZZO T, TOPAI A, et al. Recent advances on type-2 cannabinoid (CB₂)receptor agonists and their therapeutic potential[J]. Curr Med Chem, 2023, 30(12):1420-1457. doi:10.2174/0929867329666220825161603.
[20]	ROSSI F, TORTORA C, DI MARTINO M, et al. Alteration of osteoclast activity in childhood cancer survivors:Role of iron and of CB2/TRPV1 receptors[J]. PLoS One, 2022, 17(7):e271730. doi:10.1371/journal.pone.0271730.
[21]	SOPHOCLEOUS A, LANDAO-BASSONGA E, VAN'T HOF R T, et al. The type 2 cannabinoid receptor regulates bone mass and ovariectomy-induced bone loss by affecting osteoblast differentiation and bone formation[J]. Endocrinology, 2011, 152(6):2141-2149. doi:10.1210/en.2010-0930.
[22]	SOPHOCLEOUS A, IDRIS A I, RALSTON S H. Genetic background modifies the effects of type 2 cannabinoid receptor deficiency on bone mass and bone turnover[J]. Calcif Tissue Int, 2014, 94(3):259-268. doi:10.1007/s00223-013-9793-8.
[23]	BAI J, GE G, WANG Y, et al. A selective CB(2) agonist protects against the inflammatory response and joint destruction in collagen-induced arthritis mice[J]. Biomed Pharmacother, 2019, 116:109025. doi:10.1016/j.biopha.2019.109025.
[24]	BELLINI G, TORELLA M, MANZO I, et al. PKCβII-mediated cross-talk of TRPV1/CB2 modulates the glucocorticoid-induced osteoclast overactivity[J]. Pharmacol Res, 2017, 115:267-274. doi:10.1016/j.phrs.2016.11.039.
[25]	LI F, WANG F. TRPV1 in pain and itch[J]. Adv Exp Med Biol, 2021, 1349:249-273. doi:10.1007/978-981-16-4254-8_12.
[26]	LIU N, LU W, DAI X, et al. The role of TRPV channels in osteoporosis[J]. Mol Biol Rep, 2022, 49(1):577-585. doi:10.1007/s11033-021-06794-z.
[27]	WHYTE L S, RYBERG E, SIMS N A, et al. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo[J]. Proc Natl Acad Sci U S A, 2009, 106(38):16511-16516. doi:10.1073/pnas.0902743106.
[28]	MOSCA M G, MANGINI M, CIOFFI S, et al. Peptide targeting of lysophosphatidylinositol-sensing GPR55 for osteoclastogenesis tuning[J]. Cell Commun Signal, 2021, 19(1):48. doi:10.1186/s12964-021-00727-w.
[29]	MARINO S, CARRASCO G, LI B, et al. JZL184,A monoacylglycerol lipase inhibitor,induces bone loss in a multiple myeloma model of immunocompetent mice[J]. Calcif Tissue Int, 2020, 107(1):72-85. doi:10.1007/s00223-020-00689-0.
[30]	RAPHAEL-MIZRAHI B, ATTAR-NAMDAR M, CHOURASIA M, et al. Osteogenic growth peptide is a potent anti-inflammatory and bone preserving hormone via cannabinoid receptor type 2[J]. Elife, 2022, 11:e65834. doi:10.7554/eLife.65834.
[31]	MENESES C, DIOGENES A R, SIPERT C R. Endocannabinoids modulate production of osteoclastogenic factors by stem cells of the apical papilla in vitro[J]. J Endod, 2022, 48(12):1511-1516. doi:10.1016/j.joen.2022.09.005
[32]	WEI J, LI Y, LIU Q, et al. Betulinic acid protects from bone loss in ovariectomized mice and suppresses RANKL-associated osteoclastogenesis by inhibiting the MAPK and NFATc1 pathways[J]. Front Pharmacol, 2020, 11:1025. doi:10.3389/fphar.2020.01025.
[33]	ZHAO Z, NIAN M, LY H, et al. Advances in anti-osteoporosis polysaccharides derived from medicinal herbs and other edible substances[J]. Am J Chin Med, 2022, 50(2):441-470. doi:10.1142/S0192415X22500173.
[34]	XU S, FENG Y, HE W, et al. Celastrol in metabolic diseases:Progress and application prospects[J]. Pharmacol Res, 2021, 167:105572. doi:10.1016/j.phrs.2021.105572.
[35]	LIU H, ZHOU C, QI D, et al. Inhibiting monoacylglycerol lipase suppresses RANKL-induced osteoclastogenesis and alleviates ovariectomy-induced bone loss[J]. Front Cell Dev Biol, 2021, 9:640867. doi:10.3389/fcell.2021.640867.
[36]	IHN H J, KIM Y S, LIM S, et al. PF-3845,a fatty acid amide hydrolase inhibitor, directly suppresses osteoclastogenesis through ERK and NF-κB pathways in vitro and alveolar bone loss in vivo[J]. Int J Mol Sci, 2021, 22(4):1915. doi:10.3390/ijms22041915.
[37]	KHUNLUCK T, LERTSUWAN K, CHUTOE C, et al. Activation of cannabinoid receptors in breast cancer cells improves osteoblast viability in cancer-bone interaction model while reducing breast cancer cell survival and migration[J]. Sci Rep, 2022, 12(1):7398. doi:10.1038/s41598-022-11116-9.

内源性大麻素系统用于骨质疏松症预防与治疗的研究进展

Research progress of endocannabinoid system for prevention and treatment of osteoporosis

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