On the Development of Sesamoid Bones

Abstract

Sesamoid bones are a special group of small auxiliary bones that form in proximity to joints and contribute to their stability and function. Sesamoid bones display high degree of variability in size, location, penetrance and anatomical connection to the main skeleton across vertebrate species. Therefore, providing a comprehensive developmental model or classification system for sesamoid bones is challenging. Here, we examine the developmental mechanisms of three anatomically different sesamoid bones, namely patella, lateral fabella and digit sesamoids.Through a comprehensive comparative analysis at the cellular, molecular and mechanical levels, we demonstrate that all three types of sesamoid bones originated from Sox9 + /Scx + progenitors under the regulation of TGFβ and independent of mechanical stimuli from muscles. We show that BMP4 was necessary specifically for differentiation of patella but not of lateral fabella or digit sesamoids, whereas BMP2 regulated the growth of all examined sesamoids. Next, we show that whereas patella and digit sesamoids initially formed in juxtaposition to long bones, the lateral fabella formed independently at a distance. Finally, we provide evidence suggesting that while patella detached from the femur by formation of a synovial joint, digit sesamoids detached from the phalanx by a fibrocartilage joint. Collectively, these findings highlight both common and divergent molecular and mechanical features of sesamoid bone development, thereby advancing our understanding of their evolutionary plasticity.

Anatomical diversification of a skeletal novelty in bat feet

“…Consequently, differences among species in the association of the calcar with the calcaneus may be the result of relatively minor developmental alterations. Our finding of many sesamoids in bat feet, consistent with a recent assessment of bat sesamoids (Amador et al 2018), suggests a propensity for metaplastic cartilage and bone development in bat feet, as tendon metaplasia is hypothesized to play a role in sesamoid development (Sarin et al 2002; but see also Eyal et al 2015Eyal et al , 2018.…”

Sesamoids in tetrapods: the origin of new skeletal morphologies

“…The facultative appearance of sesamoids proposed herein is in line with epigenetic theory of sesamoid origins (Newman & Müller, ). Other authors have suggested that, for example, the patella, the lateral fabella and digit sesamoids could arise without a requirement for mechanical load, which may be necessary only later in development for their maintenance (Eyal et al, , a ; Márquez‐Flóres et al, ). It could be thus posited that sesamoid genesis is initiated by biochemical (genetic) signals, followed by epigenetic mechanical signals to trigger sesamoid posterior growth, conservation, and final tissue composition (see Carter et al, ).…”

“…() and Eyal et al . (, a ) contributed cellular and molecular evidence on the development of bone prominences and attachment units, placing both them and sesamoids in one category of cartilage elements developing from the same molecular chondroprogenitors ( Sox9 + / Scx + ). Koyama et al .…”

“…Much research has been performed regarding sesamoids in mammals, but unevenly distributed among clades and sesamoids. The best studied orders are Rodentia, mainly Mus musculus as a model organism (Pedersen, ; Wirtschafter & Tsujimura, ; Ralphs et al, ; Ralphs, Tyers & Benjamin, ; Doherty et al, ; Koyama et al, ; Eyal et al, , a , b ; Abella et al, ), Primates (Jungers et al, ; Walji & Fasana, ; Le Minor, , , ; Sarin et al, ), mainly focused on Homo sapiens within a clinical framework (see Section V), and Carnivora (Carey et al, ; Vaughan & France, ; McCarthy & Wood, ; Arnbjerg & Heje, ; Červený & Páral, ; Endo et al, ; Kirberger et al, ; Walker et al, ; Antón et al, ; Salesa et al, ; Abella et al, ). Surprisingly, aquatic mammals with their highly divergent skeletons have been largely ignored within the sesamoid literature.…”

“…Mammalian sesamoids that have been the subject of research by anatomists include the patella (e.g. Carey et al, ; Barnett & Lewis, ; Jungers et al, ; Holladay et al, ; Smith et al, ; Bland & Ashhurst, ; Clark & Stechschulte, ; Reese et al, ; Eyal et al, , a ; Inamassu et al, ; reviewed in Samuels et al, ), the radial sesamoid or ‘prepollex’ (see Section VI; e.g. Wood‐Jones, ; Le Minor, ; Endo et al, ; Sánchez‐Villagra & Menke, ; Antón et al, ; Salesa et al, ; Hutchinson et al, ; Mitgutsch et al, ; Abella et al, , ), the cyamella (located in the tendon of the m. popliteus) and fabellae (located in the tendon of the m. gastrocnemius) (e.g.…”