Role of Mechanical Signaling in Bone Tissue
Authors: Birks Scott Aaron 
Published: January 2025

As the global population ages and life expectancy continues to rise, osteoporosis
continues to be a growing worldwide health concern. The International
Osteoporosis Foundation reports 1 in 3 women over the age of 50 years and 1 in 5
men worldwide will experience osteoporotic fractures in their lifetime, costing
between 5 and 6.5 trillion USD annually in Canada, Europe, and the United States
alone. The need for preventative measures to reduce age-related bone loss is
clear, not only to improve quality of life for countless individuals but also to
relieve the economic burden this condition imposes.

Exercise is a proven preventative method as it increases and maintains bone
density, and reduces the risk of osteoporotic fracture with age. The benefits of
exercise are not only mediated by physiological changes, but also by
mechanically challenging the tissue. The work presented here seeks to elucidate
how attenuating cellular mechanotransduction from embryogenesis through
adolescence and into adulthood affects bone quality before and after exercise,
as well as how exposure to whole-body low-intensity vibration from adulthood
into old age affects bone quality before and after exercise.

Linker of Nucleoskeleton and Cytoskeleton (LINC) protein complexes play an
important role in cellular structure by connecting cytoskeletal elements to the
nuclear envelope, as well as being critical regulator of force transmission from
the cytoskeleton to the nucleus in vitro. We hypothesized disrupting these
complexes in vivo would lead to decreased bone quality outcomes. To investigate
LINC function in vivo, we generated two Cre/lox murine models that disrupt the
LINC complex in bone progenitor cells – one under the Prrx1 promoter and the
other under the osterix (Osx) marker. Bone microarchitecture and mechanical
properties were measured at an 8-week baseline old mice and mice subjected to a
6-week exercise intervention. We found decreased osteogenic and adipogenic
differentiation potential of bone marrow aspirates in our Osx model as well as
diminished trabecular architecture an 8-week baseline; however, there were no
remarkable changes in bone microarchitecture or mechanical properties after our
six-week running intervention. Similarly, our Prrx1 model did not show any bone
microarchitecture or mechanical property changes after our six- week running
intervention, but this model also did not show an cellular phenotype differences
or 8-week baseline differences either.

Finally, to investigate how exposure to whole-body low-intensity vibration from
adulthood into old age affects bone quality before and after exercise, we
subjected 20-week old female C57Bl/6J mice to a low-intensity vibration (LIV)
intervention (0.7g, 90Hz) for 15 minutes/2 times a day/5 days a week until they
reach 48 weeks of age. A sub-cohort was placed in a six-week running
intervention. We did not see any remarkable changes in bone microarchitecture or
bone mechanical properties with long-term LIV treatment or exercise.
Understanding the mechanical regulation of bone progenitor cells and how bone
tissue responds to long-term physical stimulation in an aging population may
lead to improved physiotherapy interventions, reducing the prevalence of
osteoporotic fractures.

The study findings included in this text, while not groundbreaking, shed light
into the complex environment of bone mechanobiology. Whole bone tissue appears
to be mostly unaffected by perturbations in mechanical signaling, whether that
be through LINC complex disruption or addition of vibrational signals throughout
the lifespan; however, there is evidence for changes in the cellular environment
which could potentially lead to bone mineral makeup differences. Future
investigation into mechanical regulation of bone tissue may benefit from
focusing on cell-specific adaptations or utilizing more robust mechanical
challenge model for induction of whole bone tissue changes.