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Ankle loading ameliorates bone loss from breast cancer–associated bone metastasis
Author(s) -
Yang Shuang,
Liu Hong,
Zhu Lei,
Li Xinle,
Liu Daquan,
Song Xiaomeng,
Yokota Hiroki,
Zhang Ping
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900306rr
Subject(s) - cathepsin k , osteoclast , osteolysis , bone resorption , endocrinology , ankle , osteoblast , medicine , bone metastasis , breast cancer , metastasis , chemistry , cancer , pathology , in vitro , dentistry , receptor , biochemistry
ABSTRACT Breast cancer is a serious health problem that preferentially metastasizes to bone. We have previously shown that bone loss can be prevented by mechanical loading, but the efficacy of ankle loading for metastasis‐linked bone loss has not been investigated. This study showed that body weight was decreased after inoculation of tumor cells, but ankle loading restored a rapid weight loss. The nonloading group exhibited a decrease in bone volume/tissue volume (BV/TV), trabecular thickness, and trabecular number (all P < 0.01) as well as an increase in trabecular separation ( P < 0.001). However, ankle loading improved those changes (all P < 0.05). Furthermore, although the nonloading group increased the tumor bearing as well as expression of IL‐8 and matrix metalloproteinase 9, ankle loading decreased them. Induction of tumor in the bone elevated the osteoclast number ( P < 0.05) as well as the levels of nuclear factor of activated T‐cells cytoplasmic 1, NF‐κB ligand, cathepsin K, and serum tartrate‐resistant acid phosphatase type 5b, but ankle loading reduced osteoclast activity and those levels (all P < 0.05). Tumor bearing was positively correlated with the osteoclast number ( P < 0.01) and negatively correlated with BV/TV and the osteoblast number (both P < 0.01). Collectively, these findings demonstrate that ankle loading suppresses tumor growth and osteolysis by inhibiting bone resorption and enhancing bone formation.—Yang, S., Liu, H., Zhu, L., Li, X., Liu, D., Song, X., Yokota, H., Zhang, P. Ankle loading ameliorates bone loss from breast cancer–associated bone metastasis. FASEB J. 33, 10742–10752 (2019). www.fasebj.org