ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass

Rafael Barreto, Yukiko Kitase, Tsutomu Matsumoto, Fabrizio Pin, Kyra C. Colston, Katherine E. Couch, Thomas M. O'Connell, Marion E. Couch, Lynda Bonewald, Andrea Bonetto

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Chemotherapy promotes the development of cachexia, a debilitating condition characterized by muscle and fat loss. ACVR2B/Fc, an inhibitor of the Activin Receptor 2B signaling, has been shown to preserve muscle mass and prolong survival in tumor hosts, and to increase bone mass in models of osteogenesis imperfecta and muscular dystrophy. We compared the effects of ACVR2B/Fc on muscle and bone mass in mice exposed to Folfiri. In addition to impairing muscle mass and function, Folfiri had severe negative effects on bone, as shown by reduced trabecular bone volume fraction (BV/TV), thickness (Tb.Th), number (Tb.N), connectivity density (Conn.Dn), and by increased separation (Tb.Sp) in trabecular bone of the femur and vertebra. ACVR2B/Fc prevented the loss of muscle mass and strength, and the loss of trabecular bone in femurs and vertebrae following Folfiri administration. Neither Folfiri nor ACVR2B/Fc had effects on femoral cortical bone, as shown by unchanged cortical bone volume fraction (Ct.BV/TV), thickness (Ct.Th) and porosity. Our results suggest that Folfiri is responsible for concomitant muscle and bone degeneration, and that ACVR2B/Fc prevents these derangements. Future studies are required to determine if the same protective effects are observed in combination with other anticancer regimens or in the presence of cancer.

Original languageEnglish (US)
Article number14470
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Bone and Bones
Drug Therapy
Muscles
Femur
Spine
Activin Receptors
Osteogenesis Imperfecta
Cachexia
Muscular Dystrophies
Porosity
Muscle Strength
Thigh
Neoplasms
Fats
Cancellous Bone
Cortical Bone

ASJC Scopus subject areas

  • General

Cite this

Barreto, R., Kitase, Y., Matsumoto, T., Pin, F., Colston, K. C., Couch, K. E., ... Bonetto, A. (2017). ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass. Scientific Reports, 7(1), [14470]. https://doi.org/10.1038/s41598-017-15040-1

ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass. / Barreto, Rafael; Kitase, Yukiko; Matsumoto, Tsutomu; Pin, Fabrizio; Colston, Kyra C.; Couch, Katherine E.; O'Connell, Thomas M.; Couch, Marion E.; Bonewald, Lynda; Bonetto, Andrea.

In: Scientific Reports, Vol. 7, No. 1, 14470, 01.12.2017.

Research output: Contribution to journalArticle

Barreto, R, Kitase, Y, Matsumoto, T, Pin, F, Colston, KC, Couch, KE, O'Connell, TM, Couch, ME, Bonewald, L & Bonetto, A 2017, 'ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass', Scientific Reports, vol. 7, no. 1, 14470. https://doi.org/10.1038/s41598-017-15040-1
Barreto R, Kitase Y, Matsumoto T, Pin F, Colston KC, Couch KE et al. ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass. Scientific Reports. 2017 Dec 1;7(1). 14470. https://doi.org/10.1038/s41598-017-15040-1
Barreto, Rafael ; Kitase, Yukiko ; Matsumoto, Tsutomu ; Pin, Fabrizio ; Colston, Kyra C. ; Couch, Katherine E. ; O'Connell, Thomas M. ; Couch, Marion E. ; Bonewald, Lynda ; Bonetto, Andrea. / ACVR2B/Fc counteracts chemotherapy-induced loss of muscle and bone mass. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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