Common cellular origin and diverging developmental programs for different sesamoid bones.

Sesamoid bones are small auxiliary bones that form near joints and contribute to their stability and function. Thus far, providing a comprehensive developmental model or classification system for this highly diverse group of bones has been challenging. Here, we compare our previously reported mechanisms of patella development in the mouse with those of two anatomically different sesamoids, namely lateral fabella and digit sesamoids. We show that all three types of sesamoid bones originate from Sox9+ /Scx+ progenitors under the regulation of TGFß and independently of mechanical stimuli from muscles. Whereas BMP2 regulates the growth of all examined sesamoids, the differentiation of lateral fabella or digit sesamoids is regulated redundantly by BMP4 and BMP2. Next, we show that whereas patella and digit sesamoids initially form in juxtaposition to long bones, lateral fabella forms independently and at a distance. Finally, our evidence suggests that, unlike the synovial joint that separates patella from femur, digit sesamoids detach from the phalanx by formation of a fibrocartilaginous joint. These findings highlight both common and divergent molecular and mechanical features of sesamoid bone development, which underscores their evolutionary plasticity.

On the development of the patella.

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 TGFß 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.

Circumventing the polydactyly 'constraint': the mole's 'thumb'.

Talpid moles across all northern continents exhibit a remarkably large, sickle-like radial sesamoid bone anterior to their five digits, always coupled with a smaller tibial sesamoid bone. A possible developmental mechanism behind this phenomenon was revealed using molecular markers during limb development in the Iberian mole (Talpa occidentalis) and a shrew (Cryptotis parva), as shrews represent the closest relatives of moles but do not show these conspicuous elements. The mole's radial sesamoid develops later than true digits, as shown by Sox9, and extends into the digit area, developing in relation to an Msx2-domain at the anterior border of the digital plate. Fgf8 expression, marking the apical ectodermal ridge, is comparable in both species. Developmental peculiarities facilitated the inclusion of the mole's radial sesamoid into the digit series; talpid moles circumvent the almost universal pentadactyly constraint by recruiting wrist sesamoids into their digital region using a novel developmental pathway and timing.

The mole's thumb -- evolution of the hand skeleton in talpids (Mammalia).

Osteological specimens representing 15 out of the 16 currently recognized talpid genera were examined and scored for seven discrete morphological characters of the hand. The phylogenetic distribution of these characters was studied in the context of alternative hypotheses of talpid relationships, using three species of shrews and a hedgehog as outgroups. All talpids show a similar number and arrangement of carpal bones. The most obvious differences concern the presence of additional sesamoid bones, the relative size of the os falciforme when present, and the degree of fusion of the scaphoid and lunate in the proximal carpal row. Marked differences in the relative length and proportions of the metacarpals also exist. The development of the carpals in Talpa europaea was studied through examination of histological sections of the hand of an embryo and a neonate. Whereas carpal anatomy in the neonate mirrors the arrangement and proportions of the adult, in the embryo the scaphoid and lunate are still separate, there are no signs of the os falciforme, and the size proportions of metacarpals to carpals are obviously different to those of the adult. A prehallux or tibial sesamoid, serial homologue to the os falciforme or prepollex (a radial sesamoid), does not have an obvious functional role, and its presence might be the result of a common epigenetic control in the hand and the foot resulting in a non-adaptive structure in the latter.

Mechanobiology and joint conformity regulate endochondral ossification of sesamoids.

Sesamoid bones form by the endochondral ossification of sesamoid cartilages. This ossification process is thought to be similar to that responsible for the formation of secondary ossific nuclei in long-bone epiphyses. Sesamoids ossify much later in development than do epiphyses, however, and bone formation within sesamoids often begins by way of multiple ossific nuclei. Endochondral growth and ossification in the formation of secondary ossific nuclei have previously been correlated with distributions of the octahedral shear and hydrostatic stresses generated in vivo within cartilage anlagen. In this study, we used two-dimensional finite element analysis to predict the distributions of octahedral shear and hydrostatic stresses in an idealized model of a sesamoid cartilage subjected to in vivo loading. We examined the influence of sesamoid joint conformity. The distribution of an osteogenic stimulus was calculated with an approach similar to that used to predict epiphyseal ossification. The results suggest that, compared with conforming joints, nonconformity between the sesamoid cartilage and its articulating surface, which arises during early development, produces higher contact pressures within the sesamoid and leads to a thicker articular cartilage layer. For a nonconforming joint surface, the results suggest that ossification is favored anywhere within a broad internal region of the sesamoid, whereas a layer at the articular surface will remain cartilaginous. These findings highlight the subtle differences between ossification processes in epiphyses and sesamoids, indicating that the mechanical stress environment in sesamoids produces a diffuse stimulus leading to the onset of ossification and that the degree of joint nonconformity may influence the thickness of the articular cartilage layer.

Coincident development of sesamoid bones and clues to their evolution.

Sesamoid bones form within tendons in regions that wrap around bony prominences. They are common in humans but variable in number. Sesamoid development is mediated epigenetically by local mechanical forces associated with skeletal geometry, posture, and muscular activity. In this article we review the literature on sesamoids and explore the question of genetic control of sesamoid development. Examination of radiographs of 112 people demonstrated that the relatively infrequent appearances of the fabella (in the lateral gastrocnemius tendon of the knee) and os peroneum (in the peroneus longus tendon of the foot) are related within individuals (P < 0.01). This finding suggests that the tendency to form sesamoids may be linked to intrinsic genetic factors. Evolutionary character analyses suggest that the formation of these sesamoids in humans may be a consequence of phylogeny. These observations indicate that variations of intrinsic factors may interact with extrinsic mechanobiological factors to influence sesamoid development and evolution.

Bipartite tibial sesamoid and hallux abducto valgus deformity: a previously unreported correlation.

A retrospective radiographic study was undertaken to determine the incidence of a bipartite tibial sesamoid and its relationship in hallux abducto valgus (HAV) deformity. It was found that the incidence of a bipartite tibial sesamoid associated with HAV deformity was twice as frequent than a bipartite tibial sesamoid in a general foot population. The authors conclude that the tibial sesamoid plays an important role in the development of HAV deformity.

The hallux sesamoids revisited.

The hallux sesamoids are vulnerable to significant injury and weight-bearing stress in both the athlete and the nonathlete. Unfortunately, they are often dismissed as inconsequential accessory bones. The historical significance, embryology, anatomy, and physiology of the sesamoids and the salient features of both traumatic and nontraumatic pathologic conditions affecting these structures are presented. Because the sesamoids can be responsible for prolonged disabling foot pain and discomfort, it is important for both clinician and radiologist to pay attention to these bones and recognize the early signs of abnormality.

Development of the navicular bone in foetal and young horses, including the arterial supply.

A macroscopic, arteriographic and histological study of the development and the arterial anatomy of the navicular bone of 33 foetuses and 55 young horses is described. After 125 days of gestation the blood supply consists of two routes: one situated in the superficial layer of the fibrocartilage and the other similar to the blood supply of the navicular bone of the normal mature horse. After 270 days gestation, the blood vessels in the fibrocartilage gradually regressed and retracted until they have disappeared at six months after birth. At two months after birth the first macroscopic thinning of the fibrocartilage was noticed. From seven months to one year about 45 per cent of the navicular bones showed a slight thinning of the fibrocartilage. A positive correlation was found between radiographic abnormalities (ie enlargement of the nutrient foramina) and the frequency of thinning of the fibrocartilage. Radiographic abnormalities were first recognised 14 days after birth, whereas the arteriogram showed the first changes such as fewer or no arteries entering distally at the distal extremities at 10 weeks after birth. At four weeks after birth the first arterial wall changes were found, ie intimal thickening with or without splitting of the internal elastic membrane. From that age onward, the number of navicular bones with arterial wall changes gradually increased. Starting at five months after birth only 6 to 20 per cent of the arteries in the navicular bones without radiographic abnormalities showed arterial wall changes. However, the navicular bones with radiographic abnormalities showed arterial wall changes in 25 to 80 per cent of the arteries.

The sesamoids of the hallux.

The seemingly innocuous tiny sesamoids play an important role in the function and pathomechanics of the hallux. The recent active participation of people of all ages in jogging and long-distance running, activities introducing repetitive stressful forces on the forefoot, induces sesamoiditis. Bones normally asymptomatic, such as the sesamoids, require renewed interest in embryology, anatomy, congenital variations, infection, osteochondritis, trauma and effective treatment.