Bone marrow is a cellular tissue that forms within the pore space and hollow diaphysis of bones. As a tissue, its primary function is to support the hematopoietic progenitor cells that maintain the populations of both erythroid and myeloid lineage cells in the bone marrow, making it an essential element of normal mammalian physiology. However, bone's primary function is load bearing, and deformations induced by external forces are transmitted to the encapsulated marrow. Understanding the effects of these mechanical inputs on marrow function and adaptation requires knowledge of the material behavior of the marrow at multiple scales, the loads that are applied, and the mechanobiology of the cells. This paper reviews the current state of knowledge of each of these factors. Characterization of the marrow mechanical environment and its role in skeletal health and other marrow functions remains incomplete, but research on the topic is increasing, driven by interest in skeletal adaptation and the mechanobiology of cancer metastasis.

Metastasis is responsible for over 90% of cancer-related deaths, and bone is the most common site for breast cancer metastasis. Metastatic breast cancer cells home to trabecular bone, which contains hematopoietic and stromal lineage cells in the marrow. As such, it is crucial to understand whether bone or marrow cells enhance breast cancer cell migration toward the tissue. To this end, we quantified the migration of MDA-MB-231 cells toward human bone in 2-D and 3 D environments. First, we found that the cancer cells cultured on tissue culture plastic migrated toward intact trabecular bone explants at a higher rate than toward marrow-deficient bone or devitalized bone. Leptin was more abundant in conditioned media from the co-cultures with intact explants, while higher levels of IL-1β, IL-6, and TNFα were detected in cultures with both intact bone and cancer cells. We further verified that the cancer cells migrated into bone marrow using a bioreactor culture system. Finally, we studied migration toward bone in 3-D gelatin. Migration speed did not depend on stiffness of this homogeneous gel, but many more dendritic-shaped cancer cells oriented and migrated toward bone in stiffer gels than softer gels, suggesting a coupling between matrix mechanics and chemotactic signals. [Media: see text] [Media: see text]