A pair of proteins, YAP and TAZ, has been identified as conductors of bone development in the womb and could provide insight into genetic diseases such as osteogenesis imperfecta, known commonly as “brittle bone disease.” This research, published in Developmental Cell and led by members of the McKay Orthopaedic Research Laboratory of the Perelman School of Medicine, adds understanding to the field of mechanobiology, which studies how mechanical forces influence biology.
“Despite more than a century of study on the mechanobiology of bone development, the cellular and molecular basis largely has remained a mystery,” says the study’s senior author, Joel Boerckel, an associate professor of orthopaedic surgery. “Here, we identify a new population of cells that are key to turning the body’s early cartilage template into bone, guided by the force-activated gene regulating proteins, YAP and TAZ.”
By combing through the genes expressed by individual cells in developing limbs, through single-cell sequencing, Boerckel and the study’s first author, former Penn Bioengineering doctoral student Joseph Collins, along with their colleagues, found and described a class of cells that they named “'vessel-associated osteoblast precursors,” which “invade” early cartilage alongside blood vessels. Since osteoblasts are the cells required to form (and fix) bones, these cells would essentially be the grandparents to bones, with osteoblasts being bones’ parents.
And, importantly, a pair of proteins called YAP and TAZ that are sensitive to the natural movement of the body—which the team’s previous work has shown is crucial to early bone development and regeneration—serve as guides to the VOPs, passing on signals they glean from the body’s mechanobiology. The researchers found that YAP and TAZ help direct blood vessel integration into the cartilage, a vital aspect of bone development.
Read more at Penn Medicine News.
