Format

Send to

Choose Destination
Sci Rep. 2017 Oct 31;7(1):14470. doi: 10.1038/s41598-017-15040-1.

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

Barreto R1, Kitase Y2,3, Matsumoto T2,3, Pin F2,3, Colston KC4, Couch KE4, O'Connell TM3,5,6,7, Couch ME3,5,6,7, Bonewald LF2,3,6,7, Bonetto A8,9,10,11,12,13.

Author information

1
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
2
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
3
Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
4
Indianapolis Project STEM, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
5
Department of Otolaryngology - Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
6
Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
7
IUPUI Center for Cachexia Research Innovation and Therapy, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
8
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. abonetto@iu.edu.
9
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. abonetto@iu.edu.
10
Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. abonetto@iu.edu.
11
Department of Otolaryngology - Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. abonetto@iu.edu.
12
Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. abonetto@iu.edu.
13
IUPUI Center for Cachexia Research Innovation and Therapy, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. abonetto@iu.edu.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center