nach oben

Erschienen in:

28.12.2022 | Original Research

Tumor Necrosis Factor-α Blunts the Osteogenic Effects of Muscle Cell-Derived Extracellular Vesicles by Affecting Muscle Cells

verfasst von: Yuto Takada, Yoshimasa Takafuji, Yuya Mizukami, Takashi Ohira, Naoyuki Kawao, Kiyotaka Okada, Hiroshi Kaji

Erschienen in: Calcified Tissue International | Ausgabe 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Extracellular vesicles (EVs) play crucial roles in physiological and pathophysiological processes. Although studies have described muscle–bone interactions via humoral factors, we reported that EVs from C2C12 muscle cells (Myo-EVs) suppress osteoclast formation. Current clinical evidence suggests that inflammation induces both sarcopenia and osteoporosis. Although tumor necrosis factor-α (TNF-α) is a critical proinflammatory factor, the influences of TNF-α on muscle–bone interactions and Myo-EVs are still unclear. In the present study, we investigated the effects of TNF-α stimulation of C2C12 cells on osteoclast formation and osteoblastic differentiation modulated by Myo-EVs in mouse cells. TNF-α significantly decreased the protein amount in Myo-EVs, but did not affect the Myo-EV size distribution. TNF-α treatment of C2C12 myoblasts significantly decreased the suppression of osteoclast formation induced by Myo-EVs from C2C12 myoblasts in mouse bone marrow cells. Moreover, TNF-α treatment of C2C12 myoblasts in mouse preosteoclastic Raw 264.7 cells significantly limited the Myo-EV-induced suppression of osteoclast formation and decreased the Myo-EV-induced increase in mRNA levels of osteoclast formation-related genes. On the other hand, TNF-α treatment of C2C12 muscle cells significantly decreased the degree of Myo-EV-promoted mRNA levels of Osterix and osteocalcin, as well as ALP activity in mouse mesenchymal ST-2 cells. TNF-α also significantly decreased miR196-5p level in Myo-EVs from C2C12 myoblasts in quantitative real-time PCR. In conclusion, TNF-α stimulation of C2C12 muscle cells blunts both the osteoclast formation suppression and the osteoblastic differentiation promotion that occurs due to Myo-EVs in mouse cells. Thus, TNF-α may disrupt the muscle–bone interactions by direct Myo-EV modulation.

Kawao N, Kaji H (2015) Interactions between muscle tissues and bone metabolism. J Cell Biochem 116(5):687–695. https://doi.org/10.1002/jcb.25040CrossRefPubMed

Kaji H (2016) Effects of myokines on bone. Bonekey Rep 5:826. https://doi.org/10.1038/bonekey.2016.48CrossRefPubMedPubMedCentral

Dam TT, Harrison S, Fink HA, Ramsdell J, Barrett-Connor E (2010) Bone mineral density and fractures in older men with chronic obstructive pulmonary disease or asthma. Osteoporos Int 21(8):1341–1349. https://doi.org/10.1007/s00198-009-1076-xCrossRefPubMed

Lee YF, Tsou HK, Leong PY, Wang YH, Wei JC (2021) Association of sepsis with risk for osteoporosis: a population-based cohort study. Osteoporos Int 32(2):301–309. https://doi.org/10.1007/s00198-020-05599-3CrossRefPubMed

Byun MK, Cho EN, Chang J, Ahn CM, Kim HJ (2017) Sarcopenia correlates with systemic inflammation in COPD. Int J Chron Obstruct Pulmon Dis 12:669–675. https://doi.org/10.2147/COPD.S130790CrossRefPubMedPubMedCentral

Kim Y (2021) Emerging treatment options for sarcopenia in chronic liver disease. Life 11(3):250. https://doi.org/10.3390/life11030250CrossRefPubMedPubMedCentral

Chu WM (2013) Tumor necrosis factor. Cancer Lett 328(2):222–225. https://doi.org/10.1016/j.canlet.2012.10.014CrossRefPubMed

Li CW, Yu K, Shyh-Chang N, Li GX, Jiang LJ, Li DJ et al (2019) Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle 10(3):586–600. https://doi.org/10.1002/jcsm.12417CrossRefPubMedPubMedCentral

Osta B, Benedetti G, Miossec P (2014) Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol 5:48. https://doi.org/10.3389/fimmu.2014.00048CrossRefPubMedPubMedCentral

10.

Zhao B (2020) Intrinsic restriction of TNF-mediated inflammatory osteoclastogenesis and bone resorption. Front Endocrinol 11:583561. https://doi.org/10.3389/fendo.2020.583561CrossRef

11.

Wang DT, Yin Y, Yang YJ, Lv PJ, Shi Y, Wei LB (2014) Resveratrol prevents TNF-α-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes. Int Immunopharmacol 19(2):206–213. https://doi.org/10.1016/j.intimp.2014.02.002CrossRefPubMed

12.

Cui Y, Luan J, Li H, Zhou X, Han J (2016) Exosomes derived from mineralizing osteoblasts promote ST2 cell osteogenic differentiation by alteration of microRNA expression. Febs Lett 590(1):185–192. https://doi.org/10.1002/1873-3468.12024CrossRef

13.

Li Q, Huang QP, Wang YL, Huang QS (2018) Extracellular vesicle-mediated bone metabolism in the bone microenvironment. J Bone Miner Metab 36(1):1–11. https://doi.org/10.1007/s00774-017-0860-5CrossRefPubMed

14.

Sun W, Zhao C, Li Y, Wang L, Nie G, Li Y et al (2016) Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity. Cell Discov 2(1):1–23. https://doi.org/10.1038/celldisc.2016.15CrossRef

15.

Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Suzuki H et al (2018) Coupling of bone resorption and formation by RANKL reverse signalling. Nature 561(7722):195–200. https://doi.org/10.1038/s41586-018-0482-7CrossRefPubMed

16.

Uenaka M, Yamashita E, Kikuta J, Morimoto A, Ochiya T, Ishii M et al (2022) Osteoblast-derived vesicles induce a switch from bone-formation to bone-resorption in vivo. Nat Commun 13(1):1–13. https://doi.org/10.1038/s41467-022-28673-2CrossRef

17.

Qin Y, Peng Y, Zhao W, Pan J, Ksiezak-Reding H, Cardozo C, Qin W et al (2017) Myostatin inhibits osteoblastic differentiation by suppressing osteocyte-derived exosomal microRNA-218: A novel mechanism in muscle-bone communication. J Biol Chem 292(26):11021–11033. https://doi.org/10.1074/jbc.M116.770941CrossRefPubMedPubMedCentral

18.

Takafuji Y, Tatsumi K, Ishida M, Kawao N, Okada K, Kaji H (2020) Extracellular vesicles secreted from mouse muscle cells suppress osteoclast formation: roles of mitochondrial energy metabolism. Bone 134:115298. https://doi.org/10.1016/j.bone.2020.115298CrossRefPubMed

19.

Takafuji Y, Tatsumi K, Kawao N, Okada K, Muratani M, Kaji H (2021) Effects of fluid flow shear stress to mouse muscle cells on the bone actions of muscle cell-derived extracellular vesicles. PLoS One 16(5):e0250741. https://doi.org/10.1371/journal.pone.0250741CrossRefPubMedPubMedCentral

20.

Xu J, Feng Y, Jeyaram A, Jay SM, Zou L, Chao W (2018) Circulating plasma extracellular vesicles from septic mice induce inflammation via microRNA-and TLR7-dependent mechanisms. J Immunol 201(11):3392–3400. https://doi.org/10.4049/jimmunol.1801008CrossRefPubMedPubMedCentral

21.

Cheng M, Yang J, Zhao X, Zeng Q, Yu Y, Qin G et al (2019) Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells. Nat Commun 10(1):1–9. https://doi.org/10.1038/s41467-019-08895-7CrossRef

22.

Kang M, Huang CC, Lu Y, Shirazi S, Ravindran S, Cooper LF (2022) Extracellular vesicles from TNFα preconditioned MSCs: Effects on immunomodulation and bone regeneration. Front. Immunol 13:878194. https://doi.org/10.3389/fimmu.2022.878194CrossRefPubMedPubMedCentral

23.

Takafuji Y, Hori M, Mizuno T, Harada-Shiba M (2019) Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr^−/− mice. Cardiovasc Res 115(6):1041–1051. https://doi.org/10.1093/cvr/cvy271CrossRefPubMed

24.

Forterre A, Jalabert A, Chikh K, Pesenti S, Granjon A, Rome S et al (2014) Myotube-derived exosomal miRNAs downregulate Sirtuin1 in myoblasts during muscle cell differentiation. Cell Cycle 13(1):78–89. https://doi.org/10.4161/cc.26808CrossRefPubMed

25.

Chen L, Yao X, Yao H, Ji Q, Ding G, Liu X (2020) Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells. FASEB J 34(4):5178–5192. https://doi.org/10.1096/fj.201902307RRRCrossRefPubMed

26.

Sohda M, Misumi Y, Oda K (2015) TNFα triggers release of extracellular vesicles containing TNFR1 and TRADD, which can modulate TNFα responses of the parental cells. Arch Biochem Biophys 587:31–37. https://doi.org/10.1016/j.abb.2015.10.009CrossRefPubMed

27.

Legros V, Jeannin P, Chaze T, Gianetto QG, Butler-Browne G, Ceccaldi PE et al (2020) Differentiation-dependent susceptibility of human muscle cells to Zika virus infection. PLoS Negl Trop Dis 14(8):e0008282. https://doi.org/10.1371/journal.pntd.0008282CrossRefPubMedPubMedCentral

28.

Sanvee GM, Bouitbir J, Krahenbuhl S (2021) C2C12 myoblasts are more sensitive to the toxic effects of simvastatin than myotubes and show impaired proliferation and myotube formation. Biochem Pharmacol 190:114649. https://doi.org/10.1016/j.bcp.2021.114649CrossRefPubMed

29.

Takafuji Y, Tatsumi K, Kawao N, Okada K, Muratani M, Kaji H (2021) MicroRNA-196a-5p in extracellular vesicles secreted from myoblasts suppresses osteoclast-like cell formation in mouse cells. Calcif Tissue Int 108(3):364–376. https://doi.org/10.1007/s00223-020-00772-6CrossRefPubMed

30.

Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS (2009) miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 24(5):816–825. https://doi.org/10.1359/jbmr.081230CrossRefPubMed

31.

Candini O, Spano C, Murgia A, Grisendi G, Piccinno MS, Dominici M et al (2015) Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis. Stem Cells 33(3):939–950. https://doi.org/10.1002/stem.1897CrossRefPubMed

32.

Gu Y, Ma L, Song L, Li X, Chen D, Bai X (2017) miR-155 inhibits mouse osteoblast differentiation by suppressing SMAD5 expression. BioMed Res Int 2017:1893520. https://doi.org/10.1155/2017/1893520CrossRefPubMedPubMedCentral

33.

Zhao H, Zhang J, Shao H, Liu J, Chen J, Huang Y et al (2017) Transforming growth factor β1/Smad4 signaling affects osteoclast differentiation via regulation of miR 155 expression. Mol Cells 40(3):211–221. https://doi.org/10.1434/molcells.2017.2303CrossRefPubMedPubMedCentral

Titel: Tumor Necrosis Factor-α Blunts the Osteogenic Effects of Muscle Cell-Derived Extracellular Vesicles by Affecting Muscle Cells
verfasst von: Yuto Takada
Yoshimasa Takafuji
Yuya Mizukami
Takashi Ohira
Naoyuki Kawao
Kiyotaka Okada
Hiroshi Kaji
Publikationsdatum: 28.12.2022
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 3/2023
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-022-01056-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Tumor Necrosis Factor-α Blunts the Osteogenic Effects of Muscle Cell-Derived Extracellular Vesicles by Affecting Muscle Cells

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2023

Causal Effects of Plasma Proteome on Osteoporosis and Osteoarthritis

Diagnostic Approach to Patients with Low Serum Alkaline Phosphatase

Reference Intervals for Bone Impact Microindentation in Healthy Adults: A Multi-Centre International Study

Effects of Infantile Hypophosphatasia on Human Dental Tissue

Extensive and Differential Deterioration of Hip Muscles May Preexist in Older Adults with Hip Fractures: Evidence from a Cross-Sectional Study

Comparing the Fracture Profile of Osteosarcopenic Older Adults with Osteopenia/Osteoporosis Alone

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin