Mechanical Forces Regulate Plasticity of Scx+ Cells During Condyle Growth

Objectives: The temporomandibular joint (TMJ) is the most complex joint in the human body with abundant tendon attachments. It’s well established that mechanical force directly regulates the development of TMJ condyle, but the mechanism is unclear. The aim of this study was to determine the regulatory role of mechanical loading on the growth of the TMJ condyle postnatally via the transdifferentiation of tendon cells to chondrocytes and osteocytes.
Methods: Mice from the R26RtdTomato; Scx-Cre line were used with Botox injection into their superficial masseter twice per week from 2-week-old until harvested at 9 weeks. To determine the effect on tendon cell transdifferentiation due to mechanical loading, in vivo cell lineage tracing, radiology, histology, and immunohistochemistry were used.
Results: The key findings are: 1) the TMJ condyle is composed of a well-established cartilage head and an overlooked “bony head” that grows after birth and continuously expands throughout life; 2) tendon cells transdifferentiate into chondrocytes thereby directly participating in cartilage head formation; 3) furthermore, tendon cells also transdifferentiate into bone cells via an interface and contribute to bony head formation; 4) radiologic and histologic analyses showed drastic decreases in the bone volume, size, and mineral level of the bony head after Botox injections; 5) the cartilage head and bony head had a 54% and 90% reduction, respectively, in Scx+ chondrocytes and osteocytes in the botoxed condyle compared to WT; 6) moreover, the interface and bony condyle head showed 54% and 60% less Osx expression in Scx+ lineage, respectively, compared to the WT condyle, giving more support to the view of tendon cell transdifferentiation being regulated by loading.
Conclusions: Mechanical force due to muscle contraction is the driving regulator of condylar development via the direct transdifferentiation of tendon cells into cartilage or bone.