On the development of the patella

Abstract

The current view of skeletal patterning fails to explain the formation of sesamoid bones. These small bones, which facilitate musculoskeletal function, are exceptionally embedded within tendons. Although their structural design has long puzzled researchers, only a limited model for sesamoid bone development has emerged. To date, sesamoids are thought to develop inside tendons in response to mechanical signals from the attaching muscles. However, this widely accepted model has lacked substantiation. Here, we show that, contrary to the current view, in the mouse embryo the patella initially develops as a bony process at the anteriodistal surface of the femur. Later, the patella is separated from the femur by a joint formation process that is regulated by mechanical load. Concurrently, the patella becomes superficially embedded within the quadriceps tendon. At the cellular level, we show that, similar to bone eminences, the patella is formed secondarily by a distinct pool of Sox9-and Scx-positive progenitor cells. Finally, we show that TGFβ signaling is necessary for the specification of patella progenitors, whereas the BMP4 pathway is required for their differentiation. These findings establish an alternative model for patella development and provide the mechanical and molecular mechanisms that underlie this process. More broadly, our finding that activation of a joint formation program can be used to switch between the formation of bony processes and of new auxiliary bones provides a new perspective on plasticity during skeletal patterning and evolution.

Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system

“…Scx is also transiently expressed in Sox9 -expressing entheseal and sesamoid cartilage during early stages of chondrogenic differentiation, as previously reported1337. This is consistent with our previous findings from lineage analysis using ScxCre transgenic mice that entheseal and patella chondroprogenitors were positive for Scx 3.…”

Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis

“…The largest reduction in mineral apposition was seen in the proximal enthesis of the PT. Since this ScxCre model has been shown to target the primary cartilage of the patella as well as the PT (Blitz, et al 2013; Eyal, et al 2015), this model may have had a combinatory effect leading to the largest reduction in this enthesis. These severe reductions in mineral apposition are consistent with prior reports examining the role of Hh signaling in enthesis development (Schwartz, et al 2015; Breidenbach, et al 2015).…”

Evolution of the patellar sesamoid bone in mammals

“…rabbits, rats, mice, humans Bland & Ashhurst, 1997; Clark & Stechschulte, 1998; Patton & Kaufman, 1995; Spark & Dawson, 1928; Tria & Alicea, 1995; Walmsley, 1940). Very recently, the development of the patella in mouse embryos was re-examined and the claim made that the patella develops as a process that branches off the femur, strongly influenced by mechanical loading in that region (Eyal et al, 2015). Whether this truly happens as described in mice, let alone other mammals, and whether it can be accepted as unexpected support for the “traction epiphysis” origin of patellar sesamoids (e.g.…”