Ankle loading ameliorates bone loss from breast cancer–associated bone metastasis

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). http://www.fasebj.org

Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β‐catenin signaling

“…Since bone is a mechano‐sensitive organ, moderate pulsating loading, oscillatory compressive loads, can be applied to various synovial joints in a form of elbow loading, knee loading and ankle loading . Joint loading can change intramedullary pressure of bone cavities.…”

“…Since bone is a mechano-sensitive organ, moderate pulsating loading, oscillatory compressive loads, can be applied to various synovial joints in a form of elbow loading, knee loading and ankle loading. [17][18][19][20] Joint loading can change intramedullary pressure of bone cavities. The moderately changing pressure may generate fluid flow in a lacuna canalicular network in bone cortex, and activate anabolic genes in bone.…”

Mechanical Loading Prevents Obesity-Associated Bone Loss by Maintaining the Balance between Adipocytes and Osteoblasts

“…Using H&E stained femoral sections, we determined A.ar/T.ar (in %, T.ar = total tissue area, and A.ar = adipocytes area), adipocyte perimeter, adipocyte number [30] and B.ar/T.ar (in %, T.ar = total tissue area, and B.ar = trabecular bone area), as well as bone trabecular circumference in the 1.9 mm 2 sample area of the proximal femoral growth plate [31]. Furthermore, MacNeal's stained sections were used to determine the osteoblast number on the trabecular bone surface (osteoblasts number/bone surface, N.Ob/BS/mm) [32].…”

Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR‐214‐3p from bone marrow‐derived mesenchymal stem cells

“…13 We have developed joint loading modalities, 14 in which dynamic lateral loads are applied to synovial joints such as the elbow, 15 knee, 16 and ankle. 17,18 It is considered that mechanical loading induces dynamic deformation in the epiphysis that drives the alteration in intramedullary pressure in the medullary cavity and interstitial fluid flow in the lacunocanalicular network. 14 We previously reported that knee loading stimulated wound healing in the femoral neck and tibia, 19,20 prevented cartilage degeneration, 21,22 and promoted vessel remodeling and bone healing in osteoporosis of the femoral head.…”