Soluble RANKL exaggerates hindlimb suspension-induced osteopenia but not muscle protein balance.

We examined the hypothesis that exaggerating unloading-induced bone loss using a combination of hindlimb suspension (HLS) and exogenous injections of receptor activator of nuclear factor-κB ligand (RANKL) also exaggerates gastrocnemius and quadriceps muscle loss. Forty, male C57Bl/6J mice (16 weeks) were subjected to HLS or normal ambulation (ground control, GC) for 14 days. Mice received three intraperitoneal injections of either human recombinant soluble RANKL or phosphate-buffered saline as control (n = 10/group) at 24 h intervals starting on Day 1 of HLS.

Combined Hind Limb Suspension and sRANK-L on Bone Strength in Mice by Finite Element Analysis: Effects of Anatomic Model Height.

With commercial space travel on the horizon, it is important to understand how the microgravity environment of space effects bone strength. The reduction in skeletal loading is known to cause a rapid loss in bone density. How this corresponds to losses of bone strength is not well known, especially when combined with the osteoporotic effects of aging.

The Effects of Hind Limb Suspension and Cast Mediated Immobilization on Bone Strength Properties.

Astronauts and patients on bedrest are subject to a combination of bone strength losses and muscle atrophy due to microgravity and unloading. In this study, mice were subject to both hind limb suspension and cast mediated immobilization. Pre-treatment and post-treatment microCT scans were utilized to create finite element models.

Combination of hindlimb suspension and immobilization by casting exaggerates sarcopenia by stimulating autophagy but does not worsen osteopenia.

Astronauts in space experience a unique environment that causes the concomitant loss of bone and muscle. However, the interaction between these tissues and how osteopenia and sarcopenia affect each other is unclear. We explored this relationship by exaggerating unloading-induced muscle loss using a unilateral casting model in conjunction with hindlimb suspension (HLS).

Simulated space radiation sensitizes bone but not muscle to the catabolic effects of mechanical unloading.

Deep space travel exposes astronauts to extended periods of space radiation and mechanical unloading, both of which may induce significant muscle and bone loss. Astronauts are exposed to space radiation from solar particle events (SPE) and background radiation referred to as galactic cosmic radiation (GCR). To explore interactions between skeletal muscle and bone under these conditions, we hypothesized that decreased mechanical load, as in the microgravity of space, would lead to increased susceptibility to space radiation-induced bone and muscle loss.

Cx43 and mechanotransduction in bone.

Bone adaptation to changes in mechanical stimuli occurs by adjusting bone formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone mass. Osteocytes coordinate the actions of these cells on the bone surface by sensing mechanical forces and producing cytokines that increase or prevent osteoblast and osteoclast differentiation and function. Channels formed by connexins (Cxs) and, in particular, connexin 43 (Cx43) in osteoblasts and osteocytes are central part of this mechanism to control bone mass.