Hypergravity as a gravitational therapy mitigates the effects of knee osteoarthritis on the musculoskeletal system in a murine model

Abstract

Insights into the effects of osteoarthritis (OA) and physical interventions on the musculoskeletal system are limited. Our goal was to analyze musculoskeletal changes in OA mice and test the efficacy of 8-week exposure to hypergravity, as a replacement of physical activity. 16-week-old male (C57BL/6J) mice allocated to sham control and OA groups not centrifuged (Ctrl 1g and OA 1g, respectively) or centrifuged at 2g acceleration (Ctrl 2g and OA 2g). OA 1g displayed decreased trabecular bone in the proximal tibia metaphysis and increased osteoclastic activity and local TNFα gene expression, all entirely prevented by 2g gravitational therapy. However, while cortical bone of tibia midshaft was preserved in OA 1g (vs. ctrl), it is thinner in OA 2g (vs. OA 1g). In the hind limb, OA at 1g increased fibers with lipid droplets by 48% in the tibialis anterior, a fact fully prevented by 2g. In Ctrl, 2g increased soleus, tibialis anterior and gastrocnemius masses. In the soleus of both Ctrl and OA, 2g induced larger fibers and a switch from type-II to type-I fiber. Catabolic (myostatin and its receptor activin RIIb and visfatine) and anabolic (FNDC5) genes dramatically increased in Ctrl 2g and OA 2g (p<0.01 vs 1g). Nevertheless, the overexpression of FNDC5 (and follistatine) was smaller in OA 2g than in Ctrl 2g. Thus, hypergravity in OA mice produced positive effects for trabecular bone and muscle typology, similar to resistance exercises, but negative effects for cortical bone.

Gravitational Experimental Platform for Animal Models, a New Platform at ESA’s Terrestrial Facilities to Study the Effects of Micro- and Hypergravity on Aquatic and Rodent Animal Models

“…Thus, combining drug administration with hypergravity exposure could potentially be a strategy to improve drug efficacy. It has also been shown that hypergravity has positive effects on trabecular bone and muscle typology in osteoarthritic mice [ 103 ]. These effects were similar to those induced by resistance exercises, but negative effects were noted for cortical bone.…”

Hypergravity Load Modulates Acetaminophen Nephrotoxicity via Endoplasmic Reticulum Stress in Association with Hepatic microRNA-122 Expression

“…Exposure to spaceflight conditions could result in physical and physiological stress due to gravitational alterations [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. The greatest gravitational change that living organisms experience during escape and re-entry into the Earth’s atmosphere is the high gravity applied during the ascent of the launch vehicle and the rapid change to weightlessness experienced thereafter.…”