Mesenchymal and mechanical mechanisms of secondary cartilage induction

Abstract

Secondary cartilage occurs at articulations, sutures, and muscle attachments, and facilitates proper kinetic movement of the skeleton. The induction and maintenance of secondary cartilage requires mechanical stimulation and accordingly, its evolutionary presence or absence reflects species-specific variation in functional anatomy. Avians illustrate this point well. In conjunction with their distinct adult mode of feeding via levered straining, duck develop a pronounced secondary cartilage at the insertion (i.e., enthesis) of the mandibular adductor muscles on the lower jaw skeleton. An equivalent cartilage is absent in quail, which peck at their food. We hypothesized that species-specific pattern and a concomitant dissimilarity in the local mechanical environment promote secondary chondrogenesis in the mandibular adductor enthesis of duck versus quail. To test our hypothesis we employed two experimental approaches. First, we transplanted neural crest mesenchyme (NCM) from quail into duck, which produced chimeric “quck” with a jaw complex resembling that of quail, including an absence of enthesis secondary cartilage. Second, we modified the mechanical environment in embryonic duck by paralyzing skeletal muscles, and by blocking the ability of NCM to support mechanotransduction through stretch-activated ion channels. Paralysis inhibited secondary cartilage, as evidenced by changes in histology and expression of genes that affect chondrogenesis, including members of the FGF and BMP pathways. Ion channel inhibition did not alter enthesis secondary cartilage but caused bone to form in place of secondary cartilage at articulations. Thus, our study reveals that enthesis secondary cartilage forms through mechanisms that are distinct from those regulating other secondary cartilage. We conclude that by directing the musculoskeletal patterning and integration of the jaw complex, NCM modulates the mechanical forces and molecular signals necessary to control secondary cartilage formation during development and evolution.

Low-Frequency Mechanical Stimulation Modulates Osteogenic Differentiation of C2C12 Cells

“…These findings are consistent with those of previous studies involving significantly different mechanical conditions, notably higher oscillatory stimulation frequencies [26][27][28]. These previous studies employed frequencies between 0.1 and 1 Hz to show that mechanical stimulation can inhibit or induce stem cell differentiation to desired lineages [29][30][31][32][33]. The present results show that this upregulation in bone marker genes can also occur at frequencies as low as 0.01 Hz, which are much lower than fundamental frequencies of locomotion.…”

Assessing Species-specific Contributions To Craniofacial Development Using Quail-duck Chimeras

“…Interactions between the donor neural crest cells and surrounding host-derived tissues that underlie proper histogenesis and morphogenesis of the craniofacial complex have previously been extensively studied. In particular, neural crest mesenchyme directs species-specific morphology of the face 7,13,51,59 , feather pattern 52 , muscle pattern 56 , and cartilage 53,57 through the regulation of host gene expression. For example, neural crest mesenchyme dictates when bone forms in the mandible by temporally regulating Bmp4 expression 55 .…”

Craniofacial morphology in Turner syndrome patientstreated with growth hormone

“…On the other hand, mandibular ramus was overgrown in comparison to mandibular corpus most probably due to bone apposition on secondary mandibular condylar cartilage. 32 Increased length of mandibular ramus, in combination with the average length of posterior cranial base, was considered to contribute to increased facial heights in study group. 18,19,21 The ratio between posterior and anterior facial height indicated that the effects were more pronounced on posterior facial height.…”