Skip to main content
Erschienen in: Current Osteoporosis Reports 1/2017

04.02.2017 | Kidney and Bone (S Moe and I Salusky, Section Editors)

The Role of TGFβ in Bone-Muscle Crosstalk

verfasst von: Jenna N. Regan, Trupti Trivedi, Theresa A. Guise, David L. Waning

Erschienen in: Current Osteoporosis Reports | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

The role of bone-derived factors in regulation of skeletal muscle function is an important emerging aspect of research into bone-muscle crosstalk. Implications for this area of research are far reaching and include understanding skeletal muscle weakness in cancer, osteoporosis, cachexia, rare diseases of bone, and aging.

Recent Findings

Recent research shows that bone-derived factors can lead to changes in the skeletal muscle. These changes can either be anabolic or catabolic, and we focus this review on the role of TGFβ in driving oxidative stress and skeletal muscle weakness in the setting of osteolytic cancer in the bone.

Summary

The bone is a preferred site for breast cancer metastasis and leads to pathological bone loss. Osteolytic cancer in the bone leads to release of TGFβ from the bone via osteoclast-mediated bone destruction. Our appreciation of crosstalk between the muscle and bone has recently expanded beyond mechanical force-driven events to encompass a variety of signaling factors originating in one tissue and communicating to the other. This review summarizes some previously known mediators of bone-to-muscle signaling and also recent work identifying a new role for bone-derived TGFβ as a cause of skeletal muscle weakness in the setting of osteolytic cancer in the bone. Multiple points of potential therapeutic intervention are discussed.
Literatur
1.
Zurück zum Zitat Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsbrun M. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-sepharose. J Biol Chem. 1986;261(27):12665–74.PubMed Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsbrun M. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-sepharose. J Biol Chem. 1986;261(27):12665–74.PubMed
5.
Zurück zum Zitat • Levinger I, Scott D, Nicholson GC, Stuart AL, Duque G, McCorquodale T, et al. Undercarboxylated osteocalcin, muscle strength and indices of bone health in older women. Bone. 2014;64:8–12. doi:10.1016/j.bone.2014.03.008. This study shows an age-adjusted association between lower limb strength and osteocalcin in humansCrossRefPubMed • Levinger I, Scott D, Nicholson GC, Stuart AL, Duque G, McCorquodale T, et al. Undercarboxylated osteocalcin, muscle strength and indices of bone health in older women. Bone. 2014;64:8–12. doi:10.​1016/​j.​bone.​2014.​03.​008. This study shows an age-adjusted association between lower limb strength and osteocalcin in humansCrossRefPubMed
10.
Zurück zum Zitat Wildemann B, Kadow-Romacker A, Haas NP, Schmidmaier G. Quantification of various growth factors in different demineralized bone matrix preparations. J Biomed Mater Res A. 2007;81(2):437–42. doi:10.1002/jbm.a.31085.CrossRefPubMed Wildemann B, Kadow-Romacker A, Haas NP, Schmidmaier G. Quantification of various growth factors in different demineralized bone matrix preparations. J Biomed Mater Res A. 2007;81(2):437–42. doi:10.​1002/​jbm.​a.​31085.CrossRefPubMed
12.
Zurück zum Zitat Blaauw B, Canato M, Agatea L, Toniolo L, Mammucari C, Masiero E, et al. Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. FASEB J. 2009;23(11):3896–905. doi:10.1096/fj.09-131870.CrossRefPubMed Blaauw B, Canato M, Agatea L, Toniolo L, Mammucari C, Masiero E, et al. Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. FASEB J. 2009;23(11):3896–905. doi:10.​1096/​fj.​09-131870.CrossRefPubMed
13.
Zurück zum Zitat •• Sartori R, Schirwis E, Blaauw B, Bortolanza S, Zhao J, Enzo E, et al. BMP signaling controls muscle mass. Nat Genet. 2013;45(11):1309–18. doi:10.1038/ng.2772. This paper describes the role of BMPs in maintenance of the muscle. Signaling through SMAD1/5/8 causes muscle hypertrophy and counteracts muscle atrophy signals through regulation of ubiquitin-mediated protein degradationCrossRefPubMed •• Sartori R, Schirwis E, Blaauw B, Bortolanza S, Zhao J, Enzo E, et al. BMP signaling controls muscle mass. Nat Genet. 2013;45(11):1309–18. doi:10.​1038/​ng.​2772. This paper describes the role of BMPs in maintenance of the muscle. Signaling through SMAD1/5/8 causes muscle hypertrophy and counteracts muscle atrophy signals through regulation of ubiquitin-mediated protein degradationCrossRefPubMed
16.
17.
Zurück zum Zitat Ajubi NE, Klein-Nulend J, Nijweide PJ, Vrijheid-Lammers T, Alblas MJ, Burger EH. Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes—a cytoskeleton-dependent process. Biochem Biophys Res Commun. 1996;225(1):62–8. doi:10.1006/bbrc.1996.1131.CrossRefPubMed Ajubi NE, Klein-Nulend J, Nijweide PJ, Vrijheid-Lammers T, Alblas MJ, Burger EH. Pulsating fluid flow increases prostaglandin production by cultured chicken osteocytes—a cytoskeleton-dependent process. Biochem Biophys Res Commun. 1996;225(1):62–8. doi:10.​1006/​bbrc.​1996.​1131.CrossRefPubMed
18.
Zurück zum Zitat Kitase Y, Barragan L, Qing H, Kondoh S, Jiang JX, Johnson ML, et al. Mechanical induction of PGE2 in osteocytes blocks glucocorticoid-induced apoptosis through both the beta-catenin and PKA pathways. J Bone Miner Res. 2010;25(12):2657–68. doi:10.1002/jbmr.168.CrossRefPubMedPubMedCentral Kitase Y, Barragan L, Qing H, Kondoh S, Jiang JX, Johnson ML, et al. Mechanical induction of PGE2 in osteocytes blocks glucocorticoid-induced apoptosis through both the beta-catenin and PKA pathways. J Bone Miner Res. 2010;25(12):2657–68. doi:10.​1002/​jbmr.​168.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Harada SI, Balena R, Rodan GA, Rodan SB. The role of prostaglandins in bone formation. Connect Tissue Res. 1995;31(4):279–82.CrossRefPubMed Harada SI, Balena R, Rodan GA, Rodan SB. The role of prostaglandins in bone formation. Connect Tissue Res. 1995;31(4):279–82.CrossRefPubMed
20.
Zurück zum Zitat Mo C, Romero-Suarez S, Bonewald L, Johnson M, Brotto M. Prostaglandin E2: from clinical applications to its potential role in bone-muscle crosstalk and myogenic differentiation. Recent Pat Biotechnol. 2012;6(3):223–9.CrossRefPubMedPubMedCentral Mo C, Romero-Suarez S, Bonewald L, Johnson M, Brotto M. Prostaglandin E2: from clinical applications to its potential role in bone-muscle crosstalk and myogenic differentiation. Recent Pat Biotechnol. 2012;6(3):223–9.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Aono Y, Hasegawa H, Yamazaki Y, Shimada T, Fujita T, Yamashita T, et al. Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res. 2011;26(4):803–10. doi:10.1002/jbmr.275.CrossRefPubMed Aono Y, Hasegawa H, Yamazaki Y, Shimada T, Fujita T, Yamashita T, et al. Anti-FGF-23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res. 2011;26(4):803–10. doi:10.​1002/​jbmr.​275.CrossRefPubMed
24.
Zurück zum Zitat Bonewald LF, Mundy GR. Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res. 1990;250:261–76. Bonewald LF, Mundy GR. Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res. 1990;250:261–76.
25.
Zurück zum Zitat • Dallas SL, Rosser JL, Mundy GR, Bonewald LF, et al. J Biol Chem. 2002;277(24):21352–60. doi:10.1074/jbc.M111663200. The release of TGFb from mineralized bone matrix is critical for normal bone remodeling and plays a large role in pathophysiological effects in the bone. This paper provides the mechanism for release of TGFb from boneCrossRefPubMed • Dallas SL, Rosser JL, Mundy GR, Bonewald LF, et al. J Biol Chem. 2002;277(24):21352–60. doi:10.​1074/​jbc.​M111663200. The release of TGFb from mineralized bone matrix is critical for normal bone remodeling and plays a large role in pathophysiological effects in the bone. This paper provides the mechanism for release of TGFb from boneCrossRefPubMed
26.
Zurück zum Zitat Sakai R, Eto Y. Involvement of activin in the regulation of bone metabolism. Mol Cell Endocrinol. 2001;180(1–2):183–8.CrossRefPubMed Sakai R, Eto Y. Involvement of activin in the regulation of bone metabolism. Mol Cell Endocrinol. 2001;180(1–2):183–8.CrossRefPubMed
27.
28.
Zurück zum Zitat •• Mendias CL, Gumucio JP, Davis ME, Bromley CW, Davis CS, Brooks SV. Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis. Muscle Nerve. 2012;45(1):55–9. doi:10.1002/mus.22232. This paper describes the role of TGFb in skeletal muscle weakness. This was the first report of muscle functional status modulation directly by TGFbCrossRefPubMedPubMedCentral •• Mendias CL, Gumucio JP, Davis ME, Bromley CW, Davis CS, Brooks SV. Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis. Muscle Nerve. 2012;45(1):55–9. doi:10.​1002/​mus.​22232. This paper describes the role of TGFb in skeletal muscle weakness. This was the first report of muscle functional status modulation directly by TGFbCrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Lam K, Chow E, Zhang L, Wong E, Bedard G, Fairchild A, et al. Determinants of quality of life in advanced cancer patients with bone metastases undergoing palliative radiation treatment. Support Care Cancer. 2013;21(11):3021–30. doi:10.1007/s00520-013-1876-6.CrossRefPubMed Lam K, Chow E, Zhang L, Wong E, Bedard G, Fairchild A, et al. Determinants of quality of life in advanced cancer patients with bone metastases undergoing palliative radiation treatment. Support Care Cancer. 2013;21(11):3021–30. doi:10.​1007/​s00520-013-1876-6.CrossRefPubMed
30.
Zurück zum Zitat Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer. 2007;110(8):1860–7. doi:10.1002/cncr.22991.CrossRefPubMed Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer. 2007;110(8):1860–7. doi:10.​1002/​cncr.​22991.CrossRefPubMed
33.
34.
39.
Zurück zum Zitat Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537–49.CrossRefPubMed Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537–49.CrossRefPubMed
40.
Zurück zum Zitat • Korpal M, Yan J, Lu X, Xu S, Lerit DA, Kang Y. Imaging transforming growth factor-beta signaling dynamics and therapeutic response in breast cancer bone metastasis. Nat Med. 2009;15(8):960–6. doi:10.1038/nm.1943. This paper describes the utility of TGFb inhibition in early bone metastases and shows that the largest source of TGFb in mice with osteolytic breast cancer bone metastases is from the mineralized bone matrixCrossRefPubMed • Korpal M, Yan J, Lu X, Xu S, Lerit DA, Kang Y. Imaging transforming growth factor-beta signaling dynamics and therapeutic response in breast cancer bone metastasis. Nat Med. 2009;15(8):960–6. doi:10.​1038/​nm.​1943. This paper describes the utility of TGFb inhibition in early bone metastases and shows that the largest source of TGFb in mice with osteolytic breast cancer bone metastases is from the mineralized bone matrixCrossRefPubMed
41.
Zurück zum Zitat Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, et al. TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 1999;103(2):197–206. doi:10.1172/JCI3523.CrossRefPubMedPubMedCentral Yin JJ, Selander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, et al. TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest. 1999;103(2):197–206. doi:10.​1172/​JCI3523.CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat •• Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC, John S, et al. Excess TGF-beta mediates muscle weakness associated with bone metastases in mice. Nat Med. 2015;21(11):1262–71. doi:10.1038/nm.3961. This paper describes the novel TGFb-Nox4-RyR1 axis that is altered in osteolytic cancer in the bone. The mechanism of muscle weakness in these studies is via increased oxidative stress and sarcoplamic reticulum calcium leakCrossRefPubMedPubMedCentral •• Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC, John S, et al. Excess TGF-beta mediates muscle weakness associated with bone metastases in mice. Nat Med. 2015;21(11):1262–71. doi:10.​1038/​nm.​3961. This paper describes the novel TGFb-Nox4-RyR1 axis that is altered in osteolytic cancer in the bone. The mechanism of muscle weakness in these studies is via increased oxidative stress and sarcoplamic reticulum calcium leakCrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Laleu B, Gaggini F, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, et al. First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J Med Chem. 2010;53(21):7715–30. doi:10.1021/jm100773e.CrossRefPubMed Laleu B, Gaggini F, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, et al. First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J Med Chem. 2010;53(21):7715–30. doi:10.​1021/​jm100773e.CrossRefPubMed
49.
Zurück zum Zitat Taniguti AP, Pertille A, Matsumura CY, Santo Neto H, Marques MJ. Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF-beta1 blocker. Muscle Nerve. 2011;43(1):82–7. doi:10.1002/mus.21869.CrossRefPubMed Taniguti AP, Pertille A, Matsumura CY, Santo Neto H, Marques MJ. Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF-beta1 blocker. Muscle Nerve. 2011;43(1):82–7. doi:10.​1002/​mus.​21869.CrossRefPubMed
Metadaten
Titel
The Role of TGFβ in Bone-Muscle Crosstalk
verfasst von
Jenna N. Regan
Trupti Trivedi
Theresa A. Guise
David L. Waning
Publikationsdatum
04.02.2017
Verlag
Springer US
Erschienen in
Current Osteoporosis Reports / Ausgabe 1/2017
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-017-0344-5

Weitere Artikel der Ausgabe 1/2017

Current Osteoporosis Reports 1/2017 Zur Ausgabe

Biomechanics (M Silva and K Jepsen, Section Editors)

Clinical Evaluation of Bone Strength and Fracture Risk

Bone and Diabetes (A Schwartz and P Vestergaard, section editors)

Is Diabetic Skeletal Fragility Associated with Microvascular Complications in Bone?

Craniofacial Skeleton (G Roberts, Section Editor)

Genetic Disorders of Dental Development: Tales from the Bony Crypt

Skeletal Development (P Trainor and K Svoboda, Section Editors)

Connexin43 and the Intercellular Signaling Network Regulating Skeletal Remodeling

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Update Orthopädie und Unfallchirurgie

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