An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6

A. Del Fattore, A. Cappariello, M. Capulli, N. Rucci, M. Muraca, F. De Benedetti, A. Teti

Research output: Contribution to journalArticle

Abstract

Summary: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory disease. Presently, no treatment regimens are available for these defects in juvenile diseases. We identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in a mouse model overexpressing IL-6. Introduction: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory diseases and have a significant impact on patients' quality of life. Presently, no treatment regimens are available for these defects in juvenile diseases. To test a new therapeutic approach, we used growing mice overexpressing the proinflammatory cytokine IL-6 (TG), which show a generalized bone loss and stunted growth. Methods: Since TG mice present increased bone resorption and impaired bone formation, we tested a combined therapy with the antiresorptive modified osteoprotegerin, Fc-OPG, and the anabolic PTH. We injected TG mice with Fc-OPG once at the 4th day of life and with hPTH(1-34) everyday from the 16th to the 30th day of age. Results: A complete prevention of growth and bone defects was observed in treated mice due to normalization of osteoclast and osteoblast parameters. Re-establishment of normal bone turnover was confirmed by RT-PCR analysis and by in vitro experiments that revealed the full rescue of osteoclast and osteoblast functions. The phenotypic recovery of TG mice was due to the sequential treatment, because TG mice treated with Fc-OPG or hPTH alone showed an increase of body weight, tibia length, and bone volume to intermediate levels between those observed in vehicle-treated WT and TG mice. Conclusions Our results identified the sequential Fc-OPG/ hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in IL-6 overexpressing mice, thus providing the proof of principle for a therapeutic approach to correct these defects in juvenile inflammatory diseases.

Original languageEnglish
Pages (from-to)681-692
Number of pages12
JournalOsteoporosis International
Volume25
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Investigational Therapies
Bone Development
Interleukin-6
Growth Disorders
Osteoclasts
Therapeutics
Osteoblasts
Osteoporosis
Chronic Disease
Teriparatide
Osteoprotegerin
Bone Remodeling
Bone Resorption
Tibia
Osteogenesis
Body Weight
Quality of Life
Cytokines
Bone and Bones
Polymerase Chain Reaction

Keywords

  • Bone loss
  • IL-6
  • Inflammatory diseases
  • Osteoporosis
  • Osteoprotegerin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6. / Del Fattore, A.; Cappariello, A.; Capulli, M.; Rucci, N.; Muraca, M.; De Benedetti, F.; Teti, A.

In: Osteoporosis International, Vol. 25, No. 2, 2014, p. 681-692.

Research output: Contribution to journalArticle

Del Fattore, A. ; Cappariello, A. ; Capulli, M. ; Rucci, N. ; Muraca, M. ; De Benedetti, F. ; Teti, A. / An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6. In: Osteoporosis International. 2014 ; Vol. 25, No. 2. pp. 681-692.
@article{112ecaf730e24c038472f2247b21fa10,
title = "An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6",
abstract = "Summary: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory disease. Presently, no treatment regimens are available for these defects in juvenile diseases. We identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in a mouse model overexpressing IL-6. Introduction: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory diseases and have a significant impact on patients' quality of life. Presently, no treatment regimens are available for these defects in juvenile diseases. To test a new therapeutic approach, we used growing mice overexpressing the proinflammatory cytokine IL-6 (TG), which show a generalized bone loss and stunted growth. Methods: Since TG mice present increased bone resorption and impaired bone formation, we tested a combined therapy with the antiresorptive modified osteoprotegerin, Fc-OPG, and the anabolic PTH. We injected TG mice with Fc-OPG once at the 4th day of life and with hPTH(1-34) everyday from the 16th to the 30th day of age. Results: A complete prevention of growth and bone defects was observed in treated mice due to normalization of osteoclast and osteoblast parameters. Re-establishment of normal bone turnover was confirmed by RT-PCR analysis and by in vitro experiments that revealed the full rescue of osteoclast and osteoblast functions. The phenotypic recovery of TG mice was due to the sequential treatment, because TG mice treated with Fc-OPG or hPTH alone showed an increase of body weight, tibia length, and bone volume to intermediate levels between those observed in vehicle-treated WT and TG mice. Conclusions Our results identified the sequential Fc-OPG/ hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in IL-6 overexpressing mice, thus providing the proof of principle for a therapeutic approach to correct these defects in juvenile inflammatory diseases.",
keywords = "Bone loss, IL-6, Inflammatory diseases, Osteoporosis, Osteoprotegerin",
author = "{Del Fattore}, A. and A. Cappariello and M. Capulli and N. Rucci and M. Muraca and {De Benedetti}, F. and A. Teti",
year = "2014",
doi = "10.1007/s00198-013-2479-2",
language = "English",
volume = "25",
pages = "681--692",
journal = "Osteoporosis International",
issn = "0937-941X",
publisher = "Springer London",
number = "2",

}

TY - JOUR

T1 - An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6

AU - Del Fattore, A.

AU - Cappariello, A.

AU - Capulli, M.

AU - Rucci, N.

AU - Muraca, M.

AU - De Benedetti, F.

AU - Teti, A.

PY - 2014

Y1 - 2014

N2 - Summary: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory disease. Presently, no treatment regimens are available for these defects in juvenile diseases. We identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in a mouse model overexpressing IL-6. Introduction: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory diseases and have a significant impact on patients' quality of life. Presently, no treatment regimens are available for these defects in juvenile diseases. To test a new therapeutic approach, we used growing mice overexpressing the proinflammatory cytokine IL-6 (TG), which show a generalized bone loss and stunted growth. Methods: Since TG mice present increased bone resorption and impaired bone formation, we tested a combined therapy with the antiresorptive modified osteoprotegerin, Fc-OPG, and the anabolic PTH. We injected TG mice with Fc-OPG once at the 4th day of life and with hPTH(1-34) everyday from the 16th to the 30th day of age. Results: A complete prevention of growth and bone defects was observed in treated mice due to normalization of osteoclast and osteoblast parameters. Re-establishment of normal bone turnover was confirmed by RT-PCR analysis and by in vitro experiments that revealed the full rescue of osteoclast and osteoblast functions. The phenotypic recovery of TG mice was due to the sequential treatment, because TG mice treated with Fc-OPG or hPTH alone showed an increase of body weight, tibia length, and bone volume to intermediate levels between those observed in vehicle-treated WT and TG mice. Conclusions Our results identified the sequential Fc-OPG/ hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in IL-6 overexpressing mice, thus providing the proof of principle for a therapeutic approach to correct these defects in juvenile inflammatory diseases.

AB - Summary: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory disease. Presently, no treatment regimens are available for these defects in juvenile diseases. We identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in a mouse model overexpressing IL-6. Introduction: Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory diseases and have a significant impact on patients' quality of life. Presently, no treatment regimens are available for these defects in juvenile diseases. To test a new therapeutic approach, we used growing mice overexpressing the proinflammatory cytokine IL-6 (TG), which show a generalized bone loss and stunted growth. Methods: Since TG mice present increased bone resorption and impaired bone formation, we tested a combined therapy with the antiresorptive modified osteoprotegerin, Fc-OPG, and the anabolic PTH. We injected TG mice with Fc-OPG once at the 4th day of life and with hPTH(1-34) everyday from the 16th to the 30th day of age. Results: A complete prevention of growth and bone defects was observed in treated mice due to normalization of osteoclast and osteoblast parameters. Re-establishment of normal bone turnover was confirmed by RT-PCR analysis and by in vitro experiments that revealed the full rescue of osteoclast and osteoblast functions. The phenotypic recovery of TG mice was due to the sequential treatment, because TG mice treated with Fc-OPG or hPTH alone showed an increase of body weight, tibia length, and bone volume to intermediate levels between those observed in vehicle-treated WT and TG mice. Conclusions Our results identified the sequential Fc-OPG/ hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in IL-6 overexpressing mice, thus providing the proof of principle for a therapeutic approach to correct these defects in juvenile inflammatory diseases.

KW - Bone loss

KW - IL-6

KW - Inflammatory diseases

KW - Osteoporosis

KW - Osteoprotegerin

UR - http://www.scopus.com/inward/record.url?scp=84899125246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899125246&partnerID=8YFLogxK

U2 - 10.1007/s00198-013-2479-2

DO - 10.1007/s00198-013-2479-2

M3 - Article

C2 - 23943168

AN - SCOPUS:84899125246

VL - 25

SP - 681

EP - 692

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

IS - 2

ER -