Update on the effects of microgravity on the musculoskeletal system

Abstract

With the reignited push for manned spaceflight and the development of companies focused on commercializing spaceflight, increased human ventures into space are inevitable. However, this venture would not be without risk. The lower gravitational force, known as microgravity, that would be experienced during spaceflight significantly disrupts many physiological systems. One of the most notably affected systems is the musculoskeletal system, where exposure to microgravity causes both bone and skeletal muscle loss, both of which have significant clinical implications. In this review, we focus on recent advancements in our understanding of how exposure to microgravity affects the musculoskeletal system. We will focus on the catabolic effects microgravity exposure has on both bone and skeletal muscle cells, as well as their respective progenitor stem cells. Additionally, we report on the mechanisms that underlie bone and muscle tissue loss resulting from exposure to microgravity and then discuss current countermeasures being evaluated. We reveal the gaps in the current knowledge and expound upon how current research is filling these gaps while also identifying new avenues of study as we continue to pursue manned spaceflight.

Fig. 1. Models for in vitro, in vivo, and flight methods for inducing microgravity.

RCCS, Clinostat, and RPM methods use rotation to create vector averaged forces to simulate microgravity. Hind limb suspension (HLS), spinal injury, and single limb immobilizationvia casting, neurectomy, or skeletal muscle paralysis (SMP) limit the ground reaction forces on the limbs by completely unloading or inducing disuse to simulate microgravity, while only HLS induces a cephalic fluid shift. Bed rest partially unloads the musculoskeletal system and induces a cephalic fluid shift when used in conjunction with head-down tilt. Parabolic flight uses rapid descent to reduce ground reaction forces and momentarily simulate microgravity. Real spaceflight removes ground reaction forces, mechanically unloading the sample or subject, and creates a cephalic fluid shift within the body.

Fig. 2. Schematic illustrating the effect of microgravity on the differentiation of stem cells into various cell lineages.

Microgravity increases commitment to the adipogenic and osteoclastic lineage while decreasing commitment to the osteoblastic, myocytic, erythrocytic, and macrophage lineages. Created using images modified from Servier Medical Art by Servier.

Fig. 3. Skeletal muscle properties obtained from mice subjected to normal loading (Control) or mechanical unloading via hindlimb suspension (Suspended).

a Total muscle mass, b muscle mass normalized to body mass, c mRNA levels of the gene encoding atrogin‐1, d mRNA levels of the gene encoding Murf1, and (e) protein synthesis rates were determined for both the gastrocnemius (top) and quadriceps (bottom). (n = 12–16/group).