image by Chang et al. of Novartis, first published in PNAS
These glowing orbs are bone cells. And they’re helping researchers understand how bone homeostasis might be achieved at the cellular tissue level.
In 2011, scientists in the Musculoskeletal Diseases group at the Novartis Institutes for BioMedical Research identified LRP4 as a novel binding partner of sclerostin, a protein that puts the brakes on bone growth. In addition, they observed LRP4 in bone-forming osteoblasts and osteocytes, cells that are presumed targets of sclerostin.
To extend on the early work, the team decided to study LRP4 and sclerostin expression in tissue from a human thigh bone. Specifically, the researchers performed co-localization staining on human femoral neck-bone sections. They generated a series of images, including the one above.
In cell culture and rodent models, the LRP4-sclerostin pair works synergistically—LRP4 enhances sclerostin’s interaction with particular cell surface receptors, enabling it to block a major pro-growth signaling pathway called WNT. The expression pattern in the image above is consistent with this hypothesis.
In the bottom left quadrant, dense, mineralized bone houses mature osteocytes, which produce and secrete sclerostin (in green). It is thought that sclerostin diffuses to the surface of the bone (here shown in the top right quadrant), where osteoblasts are laying down new bone tissue matrix. Osteoblasts at the surface and young osteocytes in the fresh matrix produce LRP4 (in red), presumably to activate the bone growth brakes by capturing sclerostin at the right time and place.