Mapping the murine TMJ glenoid fossa over development, homeostasis and in response to disease

The temporomandibular joint (TMJ) plays a key role in facilitating complex mammalian jaw movements required for daily life. It is formed between the condylar process of the mandible (or dentary bone) of the lower jaw, the glenoid (or mandibular) fossa of the squamosal/temporal bone in the upper jaw and an interposed fibrocartilage disc. Structural defects in any component of the TMJ can disrupt the entire joint, contributing to TMJ disorders. Embryonic defects in the condyle in mice have been shown to have an impact on the shape and development of the glenoid fossa, highlighting the importance of coordinated development of the two sides of the joint. Although recent research has focused on the condylar process, much less is known about the development and homeostasis of the glenoid fossa, and defects in the glenoid fossa are also evident in disease. Here, we have analysed the formation and molecular identity of the glenoid fossa using the mouse as a model. Our findings revealed distinct patterns of development of the fossa in the anterior, middle and posterior regions. Interestingly, the cartilage marker Sox9 was transiently expressed in the lateral branch of the glenoid fossa during early TMJ development, and the loss of Sox9 in Wnt1-cre;Sox9fl/fl mice resulted in the absence of this part of the fossa. Postnatal maturation of the murine glenoid fossa was marked by the initiation of a fibrocartilage layer, the formation of which coincided with the onset of independent feeding, suggesting a role for mechanical force in glenoid fossa fibrocartilage induction. In contrast to the condyle, the fossa fibrocartilage expressed low levels of FSP1, a marker of the stem/progenitor population of the condyle. Depletion of FSP1-positive cells by conditional diphtheria toxin activity in FSP1-Cre;DTA mice has previously been shown to cause a severe TMJ osteoarthritis phenotype and enlargement of the condylar head postnatally. Interestingly, here, we show that in reaction to changes in condylar shape, these mutants develop an increase in glenoid fossa angulation over time, associated with increased remodelling activity, particularly in the lateral branch of the fossa. These findings highlight that the fibrocartilage of the glenoid fossa and condyle are not equivalent and that changes in the condyle can have a knock-on secondary effect on the 3D structure of the fossa. This coordinated response would allow for alignment of the TMJ, maintaining function throughout life, even in the case of disease.