Ferroptosis and Sarcopenia-Osteoporosis after Menopause: Research Status, Traditional Chinese Medicine Strategies, and Prospects
DOI:
https://doi.org/10.53469/jcmp.2024.06(09).18Keywords:
Ferroptosis, Traditional Chinese Medicine (TCM), Sarcopenia-Osteoporosis, Postmenopausal WomenAbstract
Ferroptosis, a precisely regulated cell death mechanism, is distinguished by its intimate link to iron overload and lipid peroxidation processes, playing a pivotal role in the pathological progression of a wide range of diseases. In postmenopausal women suffering from osteoporosis, reduced muscle strength and impaired balance lead to a heightened risk of fragility fractures, markedly diminishing their quality of life. Recent groundbreaking research has underscored the crucial role of the ferroptosis mechanism in the initiation and progression of musculoskeletal diseases. This discovery not only enriches our understanding of disease mechanisms but also heralds ferroptosis pathways as novel and promising therapeutic targets for treating these conditions. Traditional Chinese Medicine (TCM) has exhibited remarkable efficacy in managing musculoskeletal diseases, with studies validating its ability to modulate ferroptosis mechanisms and profoundly impact disease regulation. This portends vast research potential and significant therapeutic promise for the future. By delving deeper into the interplay between ferroptosis and sarcopenia-osteoporosis in postmenopausal women, and by developing innovative therapeutic strategies and TCM interventions, we aspire to forge new pathways for the treatment of sarcopenia-osteoporosis in this patient population.
References
Zhang Y, Huang X, Qi B, Sun C, Sun K, Liu N, Zhu L, Wei X. Ferroptosis and musculoskeletal diseases: "Iron Maiden" cell death may be a promising therapeutic target. Front Immunol. 2022 Oct 11; 13: 972753. doi: 10.3389/fimmu.2022.972753. PMID: 36304454; PMCID: PMC9595130.
Huang Hongxing, Shi Xiaolin, Li Shenghua, et al. Expert consensus on sarcopenia-osteoporosis [J]. Chinese Journal of Osteoporosis, 2022, 28(11): 1561-1570.
Dolma S, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell. 2003 Mar;3(3):285-96.
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012 May 25;149(5):1060-72. doi: 10.1016/j.cell.2012.03.042. PMID: 22632970; PMCID: PMC3367386.
Fujimaki, M.; Furuya, N.; Saiki, S.; Amo, T.; Imamichi, Y.; Hattori, N. Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions. Mol. Cell Biol.2019,39,e00010–e00019.
Ajoolabady A, Aslkhodapasandhokmabad H, Libby P, Tuomilehto J, Lip GYH, Penninger JM, Richardson DR, Tang D, Zhou H, Wang S, Klionsky DJ, Kroemer G, Ren J. Ferritinophagy and ferroptosis in the management of metabolic diseases. Trends Endocrinol Metab. 2021 Jul;32(7):444-462. doi: 10.1016/j.tem.2021.04.010. Epub 2021 May 15. PMID: 34006412.
Liu J, Kuang F, Kroemer G, Klionsky DJ, Kang R, Tang D. Autophagy-Dependent Ferroptosis: Machinery and Regulation. Cell Chem Biol. 2020 Apr 16;27(4):420-435. doi: 10.1016/j.chembiol.2020.02.005. Epub 2020 Mar 10. PMID: 32160513; PMCID: PMC7166192.
Zhou RP, Chen Y, Wei X, Yu B, Xiong ZG, Lu C, Hu W. Novel insights into ferroptosis: Implications for age-related diseases. Theranostics. 2020 Oct26; 10(26): 11976-11997. doi: 10.7150/thno.50663. PMID: 33204324; PMCID: PMC7667696.
Cullis JO, Fitzsimons EJ, Griffiths WJ, Tsochatzis E, Thomas DW; British Society for Haematology. Investigation and management of a raised serum ferritin. Br J Haematol. 2018 May; 181(3): 331-340. doi: 10.1111/bjh.15166. Epub 2018 Apr 19. PMID: 29672840.
Zhang LL, Jiang XF, Ai HZ, Jin ZD, Xu JX, Wang B, Xu W, Xie ZG, Zhou HB, Dong QR, Xu YJ. [Relationship of iron overload to bone mass density and bone turnover in postmenopausal women with fragility fractures of the hip]. Zhonghua Wai Ke Za Zhi. 2013 Jun 1;51(6):518-21. Chinese. PMID: 24091266.
Liu LL, Liu GW, Liu H, Zhao K, Xu YJ. Iron accumulation deteriorated bone loss in estrogen-deficient rats. J Orthop Surg Res. 2021 Aug 24; 16(1):525. doi: 10.1186/s13018-021-02663-4. PMID: 34429140; PMCID: PMC8383398.
Cui J, Shibata Y, Zhu T, Zhou J, Zhang J. Osteocytes in bone aging: Advances, challenges, and future perspectives. Ageing Res Rev. 2022 May; 77:101608. doi: 10.1016/j.arr.2022.101608. Epub 2022 Mar 11. PMID: 35283289.
Ponzetti M, Rucci N. Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics. Int J Mol Sci. 2021 Jun 22; 22(13): 6651. doi:10.3390/ijms22136651. PMID: 34206294; PMCID: PMC8268587.
Chen H, Han Z, Wang Y, Su J, Lin Y, Cheng X, Liu W, He J, Fan Y, Chen L, Zuo H. Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives. J Inflamm Res. 2023 Oct 18; 16: 4661-4677. doi: 10.2147/JIR.S432111. PMID: 37872954; PMCID: PMC10590556.
Ledesma-Colunga MG, Baschant U, Fiedler IAK, Busse B, Hofbauer LC, Muckenthaler MU, Altamura S, Rauner M. Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice. Bone. 2020 Aug; 137:115400. doi: 10.1016/j. bone.2020. 115400. Epub 2020 May 4. PMID: 32380257.
Zhang H, Wang A, Li G, Zhai Q, Huang Z, Wang X, Cao Z, Liu L, Liu G, Chen B, Zhu K, Xu Y, Xu Y. Osteoporotic bone loss from excess iron accumulation is driven by NOX4-triggered ferroptosis in osteoblasts. Free Radic Biol Med. 2023 Mar;198:123-136. doi:10. 1016/j.freeradbiomed.2023.01.026. Epub 2023 Feb 3. PMID: 36738798.
Cen WJ, Feng Y, Li SS, Huang LW, Zhang T, Zhang W, Kong WD, Jiang JW. Iron overload induces G1 phase arrest and autophagy in murine preosteoblast cells. J Cell Physiol. 2018 Sep; 233(9):6779-6789. doi: 10.1002/jcp. 26405. Epub 2018 Mar 25. PMID: 29244196.
Xia D, Wu J, Xing M, Wang Y, Zhang H, Xia Y, Zhou P, Xu S. Iron overload threatens the growth of osteoblast cells via inhibiting the PI3K/AKT/FOXO3a/DUSP14 signaling pathway. J Cell Physiol. 2019 Sep; 234(9): 15668-15677. doi: 10.1002/jcp.28217. Epub 2019 Jan 29. PMID: 30693516.
Lin B, Xu J, Feng DG, Wang F, Wang JX, Zhao H. DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through activating NF-κB and MAPKs signaling pathways modulated by ROS generation. Biochem Biophys Res Commun. 2018 Jun 18;501(1):24-32. doi: 10.1016/j.bbrc.2018.04.101. Epub 2018 May 8. PMID: 29660332.
Luo C, Xu W, Tang X, Liu X, Cheng Y, Wu Y, Xie Z, Wu X, He X, Wang Q, Xiao Y, Qiu X, Tang Z, Shao G, Tu X. Canonical Wnt signaling works downstream of iron overload to prevent ferroptosis from damaging osteoblast differentiation. Free Radic Biol Med. 2022 Aug 1; 188: 337-350. doi: 10.1016/j. freeradbiomed. 2022.06.236. Epub 2022 Jun 23. PMID: 35752374.
Xu P, Lin B, Deng X, Huang K, Zhang Y, Wang N. VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis. Free Radic Biol Med. 2022 Nov20;193(Pt2):720-735.doi:10.1016/j.freeradbiomed.2022.11.013. Epub 2022 Nov 17. PMID: 36402439.
Wang B, Zhan Y, Yan L, Hao D. How zoledronic acid improves osteoporosis by acting on osteoclasts. Front Pharmacol. 2022 Aug 25; 13:961941. doi: 10.3389/fphar. 2022. 961941. PMID: 36091799; PMCID: PMC9452720.
Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H. Coupling of bone resorption and formation by RANKL reverse signalling. Nature. 2018 Sep; 561(7722):195-200. doi: 10.1038 /s41586-018-0482-7. Epub 2018 Sep 5. PMID: 30185903.
Yang J, Dong D, Luo X, Zhou J, Shang P, Zhang H. Iron Overload-Induced Osteocyte Apoptosis Stimulates Osteoclast Differentiation Through Increasing Osteocytic RANKL Production In Vitro. Calcif Tissue Int. 2020 Nov;107(5):499-509. doi: 10.1007/s00223 -020-00735-x. Epub 2020 Sep 29. PMID: 32995951.
Xue C, Luo H, Wang L, Deng Q, Kui W, Da W, Chen L, Liu S, Xue Y, Yang J, Li L, Du W, Shi Q, Li X. Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling. Front Endocrinol (Lausanne). 2023 Nov 13; 14:1234563. doi: 10.3389/fendo.2023.1234563. PMID: 38034017; PMCID: PMC10682992.
Zhang J, Zhang L, Yao G, Zhao H, Wu S. NRF2 is essential for iron-overload stimulated osteoclast differentiation through regulation of redox and iron homeostasis. Cell Biol Toxicol. 2023 Dec;39(6): 3305-3321. doi: 10.1007/s10565-023-09834-5. Epub 2023 Oct 19. PMID: 37855941.
Wang L, Fang B, Fujiwara T, Krager K, Gorantla A, Li C, Feng JQ, Jennings ML, Zhou J, Aykin-Burns N, Zhao H. Deletion of ferroportin in murine myeloid cells increasesiron accumulation and stimulates osteoclastogenesis in vitro and in vivo. J Biol Chem. 2018Jun 15;293(24):9248-9264. doi: 10.1074/jbc. RA117. 000834. Epub 2018 May 3. PMID: 29724825; PMCID: PMC6005439。
Capulli M, Paone R, Rucci N. Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys. 2014 Nov 1; 561:3-12. doi: 10.1016/j.abb.2014.05.003. Epub 2014 May 14. PMID: 24832390.
Balogh E, Tolnai E, Nagy B Jr, Nagy B, Balla G, Balla J, Jeney V. Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin. Biochim Biophys Acta. 2016 Sep;1862(9):1640-9. doi: 10.1016/j.bbadis.2016.06.003. Epub 2016 Jun 7. PMID: 27287253.
Yuan Y, Xu F, Cao Y, Xu L, Yu C, Yang F, Zhang P, Wang L, Shen G, Wang J, Xu Y. Iron Accumulation Leads to Bone Loss by Inducing Mesenchymal Stem Cell Apoptosis Through the Activation of Caspase3. Biol Trace Elem Res. 2019 Feb;187(2):434-441. doi: 10.1007/s12011-018-1388-9. Epub 2018 Jun 14. PMID: 29948914.
Komori T. Whole Aspect of Runx2 Functions in Skeletal Development. Int J Mol Sci.2022 May 21;23(10):5776. doi: 10.3390/ijms23105776. PMID: 35628587; PMCID: PMC9144571.
Li M, Yang N, Hao L, Zhou W, Li L, Liu L, Yang F, Xu L, Yao G, Zhu C, Xu W, Fang S. Melatonin Inhibits the Ferroptosis Pathway in Rat Bone Marrow MesenchymalStem Cells by Activating the PI3K / AKT / mTOR Signaling Axis to Attenuate Steroid-Induced Osteoporosis. Oxid Med Cell Longev. 2022 Aug 18; 2022: 8223737. doi: 10.1155/ 2022/ 8223737. PMID: 36035224; PMCID: PMC9410838.
Lu L, Tian L. Postmenopausal osteoporosis coexisting with sarcopenia: the role and mechanisms of estrogen. J Endocrinol. 2023 Sep 11;259(1):e230116. doi: 10.1530/ JOE-23-0116. PMID: 37523234.
Buckinx F, Aubertin-Leheudre M. Sarcopenia in Menopausal Women: Current Perspectives. Int J Womens Health. 2022 Jun 23; 14: 805-819. doi: 10.2147/ IJWH. S340537. PMID: 35769543; PMCID: PMC9235827.
Collins BC, Arpke RW, Larson AA, Baumann CW, Xie N, Cabelka CA, Nash NL, Juppi HK, Laakkonen EK, Sipilä S, Kovanen V, Spangenburg EE, Kyba M, Lowe DA. Estrogen Regulates the Satellite Cell Compartment in Females. Cell Rep. 2019 Jul 9;28(2):368-381.e6. doi: 10.1016/j.celrep.2019.06.025. PMID: 31291574; PMCID: PMC6655560.
Distefano G, Goodpaster BH. Effects of Exercise and Aging on Skeletal Muscle. Cold Spring Harb Perspect Med. 2018 Mar 1; 8(3): a029785. doi: 10.1101/ cshperspect. a029785. PMID: 28432116; PMCID: PMC5830901.
Ikeda Y, Satoh A, Horinouchi Y, Hamano H, Watanabe H, Imao M, Imanishi M, Zamami Y, Takechi K, Izawa-Ishizawa Y, Miyamoto L, Hirayama T, Nagasawa H, Ishizawa K, Aihara KI, Tsuchiya K, Tamaki T. Iron accumulation causes impaired myogenesis correlated with MAPK signaling pathway inhibition by oxidative stress. FASEB J. 2019 Aug;33(8):9551-9564. doi: 10.1096/fj.201802724RR. Epub 2019 May 30. PMID: 31145863.
Dobrowolny G, Barbiera A, Sica G, Scicchitano BM. Age-Related Alterations at Neuromuscular Junction: Role of Oxidative Stress and Epigenetic Modifications. Cells. 2021 May 24;10(6):1307. doi: 10.3390/ cells10061307. PMID: 34074012; PMCID: PMC8225025.
Huang Y, Wu B, Shen D, Chen J, Yu Z, Chen C. Ferroptosis in a sarcopenia model of senescence accelerated mouse prone 8 (SAMP8). Int J Biol Sci. 2021 Jan 1;17(1):151-162. doi: 10.7150/ijbs.53126. PMID: 33390840; PMCID: PMC7757032.
Wang Yizhe, Zhao Guoyang, Yang Jiaru. Mechanisms related to iron homeostasis imbalance and sarcopenia [J]. Chinese Journal of Osteoporosis and Bone Mineral Diseases, 2023, 16 (06): 603-608.
Skonieczna M, Cieslar-Pobuda A, Saenko Y, Foksinski M, Olinski R, Rzeszowska-Wolny J, Wiechec E. The Impact of DIDS-Induced Inhibition of Voltage - Dependent Anion Channels (VDAC) on Cellular Response of Lymphoblastoid Cells to Ionizing Radiation. Med Chem. 2017;13(5):477-483. doi: 10.2174/ 1573406413666170421102353. PMID: 28427245.
Zhao G. Is Iron Accumulation a Possible Risk Factor for Sarcopenia? Biol Trace Elem Res. 2018 Dec;186(2): 379-383. doi: 10.1007/s12011-018-1332-z. Epub 2018 Apr 5. PMID: 29623651.
Li J, Jia YC, Ding YX, Bai J, Cao F, Li F. The crosstalk between ferroptosis and mitochondrial dynamic regulatory networks. Int J Biol Sci. 2023 May 21;19(9):2756-2771. doi: 10.7150/ijbs.83348. PMID: 37324946; PMCID: PMC10266069.
Singh LP, Yumnamcha T, Devi TS. Mitophagy, Ferritinophagy and Ferroptosis in Retinal Pigment Epithelial Cells Under High Glucose Conditions: Implications for Diabetic Retinopathy and Age-Related Retinal Diseases. JOJ Ophthalmol. 2021;8(5):77-85. Epub 2021 Sep 27. PMID: 35187384; PMCID: PMC8856657.
Chen QM. Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury. Free Radic Biol Med. 2022 Feb 1; 179:133-143. doi: 10.1016/j.freeradbiomed.2021.12.001. Epub 2021 Dec 16. PMID: 34921930.
East DA, Fagiani F, Crosby J, Georgakopoulos ND, Bertrand H, Schaap M, Fowkes A, Wells G, Campanella M. PMI: a ΔΨm independent pharmacological regulator of mitophagy. Chem Biol. 2014 Nov 20;21(11):1585-96. doi: 10.1016/j.chembiol.2014.09.019. PMID: 25455860; PMCID: PMC4245710.
Jiang J, Zhao B, Xiao J, Shi L, Shang W, Shu Y, Zhao Z, Shen J, Xu J, Cai H. Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation. Phytomedicine. 2024 Jan;123:155275. doi: 10.1016/j.phymed.2023.155275. Epub 2023 Dec 12. PMID: 38142661.
Xiang S, Zhao L, Tang C, Ling L, Xie C, Shi Y, Liu W, Li X, Cao Y. Icariin inhibits osteoblast ferroptosis via Nrf2/HO-1 signaling and enhances healing of osteoporotic fractures. Eur J Pharmacol. 2024 Feb 15; 965:176244. doi: 10.1016/j.ejphar.2023.176244. Epub 2023 Dec 11. PMID: 38092316.
Li Xinchun, Hu Wanjun, Gan Farong, Ye Baofei, Wu Duoyi, Jiang Xiaobing. Protective effect and mechanism of Eucommia ulmoides-Dipsacus asperoides medicinal pair on ovariectomized rats with osteoporosis through regulating ferroptosis pathway [J]. Chinese Archives of Traditional Chinese Medicine, 2023, 41(9): 103 - 106I0036, I0037.
Ni C, Ye Q, Mi X, Jiao D, Zhang S, Cheng R, Fang Z, Fang M, Ye X. Resveratrol inhibits ferroptosis via activating NRF2/GPX4 pathway in mice with spinal cord injury. Microsc Res Tech. 2023 Oct; 86(10): 1378-1390. doi: 10.1002/jemt.24335. Epub 2023 May 2. PMID: 37129001.
Zhang Chi, Zhang Xiaoyun, Chai Yuan, et al. Proteomic analysis of the therapeutic effect of Jintiange Capsule on retinoic acid-induced osteoporotic rats [J]. Chinese Journal of Tissue Engineering Research, 2023, 27(35): 5634-5641.
Zheng Hao, Qi Xiaonan, Yao Xiaosheng. Mechanism exploration of myostatin in sarcopenia-osteoporosis under the guidance of the theory of "disharmony between muscle and bone" [J]. Chinese Journal of Osteoporosis, 2021, 27(11): 1675-1680+1693.
Li Shuanglei, Jiang Yunxia. Discussion on the relationship between sarcopenia and osteoporosis from the perspective of the theory of "disharmony between muscle and bone" [J]. Beijing Journal of Traditional Chinese Medicine, 2016, 35(06): 526-528. DOI: 10.16025/j.1674-1307.2016.06.007.
Li Yi, Chen Chongli, Zhao Mengjie, et al. Preliminary exploration of the pathogenesis and prevention and treatment strategies of sarcopenia-osteoporosis in traditional Chinese medicine [J]. Journal of Gansu University of Traditional Chinese Medicine, 2020, 37(04):38-41. DOI: 10.16841/j.issn1003-8450.2020. 04.09.
Xu L, Song X, Carroll G, You L. Novel in vitro microfluidic platform for osteocyte mechanotransduction studies. Integr Biol (Camb). 2020 Dec 30; 12(12):303-310. doi: 10.1093/intbio/zyaa025. PMID: 33420790.
Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell. 2002 Dec;3(6):889-901. doi: 10.1016/s 1534-5807 (02) 00369 -6. PMID: 12479813.
Zhang Yili, Fang Shengjie, Li Qiuyue, et al. Effects of Bugu Shengsui Recipe on oxidative stress and ferroptosis-related indicators in rats with osteoporosis [J]. Chinese Journal of Information on Traditional Chinese Medicine, 2022, 29(04): 75-79. DOI: 10.19879/j.cnki.1005-5304.202109060.
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