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Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance.

Stern T, Aviram R, Rot C, Galili T, Sharir A, Kalish Achrai N, Keller Y, Shahar R, Zelzer E - PLoS Biol. (2015)

Bottom Line: Surprisingly, our results showed that most superstructures did not drift at all.Our study reveals a general mechanism for the scaling of developing bones.More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

ABSTRACT
One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.

No MeSH data available.


Related in: MedlinePlus

Symmetry-breaking elements define longitudinal proportions in long bones.Three-dimensional reconstruction from micro-CT scans of the six limb long bones at P40. The longitudinal position of each element is indicated either by a single colored mark on the tip of the superstructure or by two colored marks at its proximal (P) and distal (D) margins, depending on the size and the morphology of the superstructure. Margins that overlap with the end of the bone or with a growth plate were not marked.
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pbio.1002212.g001: Symmetry-breaking elements define longitudinal proportions in long bones.Three-dimensional reconstruction from micro-CT scans of the six limb long bones at P40. The longitudinal position of each element is indicated either by a single colored mark on the tip of the superstructure or by two colored marks at its proximal (P) and distal (D) margins, depending on the size and the morphology of the superstructure. Margins that overlap with the end of the bone or with a growth plate were not marked.

Mentions: In each bone, anatomical points that mark the longitudinal position of superstructures, collectively referred to in the following as symmetry-breaking elements, were identified. These included the tip; the proximal and the distal margins of tuberosities, trochanters, crests, condyles, and processes; and the fusion zone of the tibiofibular complex (Fig 1). Then, the relative position of each element between the proximal and the distal ends of the bone was measured (see Materials and Methods and S1 Fig). Because the focus of this work was on longitudinal scaling, in all the analyses described in the following element positions were calculated as a function of the total bone length. As evident in Fig 2, the relative position of all elements in all bones was preserved throughout the entire growth, as the average range of deviation was 4.4%, with the exception of the tibiofibular fusion point (14.3%). These results show that longitudinal scaling in growing long bones is highly isometric.


Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance.

Stern T, Aviram R, Rot C, Galili T, Sharir A, Kalish Achrai N, Keller Y, Shahar R, Zelzer E - PLoS Biol. (2015)

Symmetry-breaking elements define longitudinal proportions in long bones.Three-dimensional reconstruction from micro-CT scans of the six limb long bones at P40. The longitudinal position of each element is indicated either by a single colored mark on the tip of the superstructure or by two colored marks at its proximal (P) and distal (D) margins, depending on the size and the morphology of the superstructure. Margins that overlap with the end of the bone or with a growth plate were not marked.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524611&req=5

pbio.1002212.g001: Symmetry-breaking elements define longitudinal proportions in long bones.Three-dimensional reconstruction from micro-CT scans of the six limb long bones at P40. The longitudinal position of each element is indicated either by a single colored mark on the tip of the superstructure or by two colored marks at its proximal (P) and distal (D) margins, depending on the size and the morphology of the superstructure. Margins that overlap with the end of the bone or with a growth plate were not marked.
Mentions: In each bone, anatomical points that mark the longitudinal position of superstructures, collectively referred to in the following as symmetry-breaking elements, were identified. These included the tip; the proximal and the distal margins of tuberosities, trochanters, crests, condyles, and processes; and the fusion zone of the tibiofibular complex (Fig 1). Then, the relative position of each element between the proximal and the distal ends of the bone was measured (see Materials and Methods and S1 Fig). Because the focus of this work was on longitudinal scaling, in all the analyses described in the following element positions were calculated as a function of the total bone length. As evident in Fig 2, the relative position of all elements in all bones was preserved throughout the entire growth, as the average range of deviation was 4.4%, with the exception of the tibiofibular fusion point (14.3%). These results show that longitudinal scaling in growing long bones is highly isometric.

Bottom Line: Surprisingly, our results showed that most superstructures did not drift at all.Our study reveals a general mechanism for the scaling of developing bones.More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

ABSTRACT
One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.

No MeSH data available.


Related in: MedlinePlus