Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice.
Elahe GanjiSyeda N LamiaMatthew StepanovichNoelle WhyteRobert W GouletAdam C AbrahamMegan L KillianPublished in: Science advances (2023)
Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure and function in response to increased loading, using optogenetically induced muscle contraction in young (i.e., growth) and adult (i.e., mature) mice. Daily bouts of unilateral optogenetic loading in young mice led to radial calcaneal expansion and warping. This also led to a weaker enthesis with increased collagen damage in young tendon and enthisis, with little change in adult mice. We then used RNA sequencing to identify the pathways associated with increased mechanical loading during growth. In tendon, we found enrichment of glycolysis, focal adhesion, and cell-matrix interactions. In bone, we found enrichment of inflammation and cell cycle. Together, we demonstrate the utility of optogenetic-induced muscle contraction to elicit in vivo adaptation of the enthesis.
Keyphrases
- skeletal muscle
- cell cycle
- high fat diet induced
- high glucose
- diabetic rats
- single cell
- oxidative stress
- bone mineral density
- drug induced
- smooth muscle
- cell proliferation
- type diabetes
- physical activity
- young adults
- cystic fibrosis
- metabolic syndrome
- cell therapy
- staphylococcus aureus
- cell migration
- high intensity
- candida albicans