How does bone know how to be the proper shape and size for development? Can we manipulate this to grow taller?
I received this email from the author regarding how distraction osteogenesis would affect how bone manipulates growth in regards to maintaining placement of superstructures: \
“It is indeed an interesting question as it challenges the system with an unnatural manipulation – i.e. interstitial growth.
The simple answer is: we haven’t tried, so I can’t say for sure.
If the relative locations of ligament and tendon insertions are what you are interested in, then previous works show that the periosteum is involved in regulation of their positions (see list below). Moreover, if the balance between proximal and distal growth rates is what you are interested in, then other works show that cross-sectional cutting and stripping of the periosteum can cause temporal acceleration in overall growth rate of the bone (also in humans, if I remember correctly), followed by a potential change in proximal to distal growth balance (I don’t think that these works test how these influence the positioning of superstructures in the bone; see list below).
Therefore, if the operation you are applying includes anchoring of the periosteum to the bone or its cutting and stripping, this is something that may influence the scaling of the bones.”
“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.”
If we can trick the bone into thinking it’s drifting maybe we can convince it to grow to maintain the position of the superstructure. For example, dislocating the bone or similar means.
Although the molecular mechanisms regulating each growth plate for different bones are similar the bones still have different elongation rates.
“superstructures, known as bone ridges, tuberosities, condyles, etc., are necessary for the attachment of tendons and ligament as well as for articulation. To perform these functions they are located at specific positions along the bone. Bone superstructures emerge during early skeletogenesis . During growth, bones elongate extensively by advancement of the two growth plates away from the superstructures. It is therefore expected that during elongation, superstructures would remain at their original position near the center of the bone. Nevertheless, the end result is proper spreading of superstructures along the mature bone, which clearly implies the existence of a morphogenetic mechanism that corrects their locations.”
It’d be interesting to see what happens to bone superstructures during distraction osteogenesis.
“An ossified bone is a rigid object and so are the superstructures protruding from it, implying that they cannot be relocated by means of cell migration or proliferation. Therefore, any scaling mechanism must be adapted to overcome these physical restrictions.”<-So we have to make the bone less rigid.
“forelimb bones tend to grow away from the elbow joint, whereas bones in hind limbs tend to grow toward the knee joint.”
” Because the periosteal sheath is stretched over the entire external surface of the bone, including both the superstructures and the growth plates, it can pass to the growth plates signals concerning the relative position of superstructures.”<-Then perhaps we can manipulate longitudinal bone growth by manipulating the periosteal sheath.
“periosteal tension down-regulates growth plate activity, as the higher the tension level, the more inhibited growth plate activity is. Damaged periosteum forms a scar tissue at the site of destruction. This scar tissue, which anchors the periosteum into the bone, creates an independent tension level near each growth plate. As a result, a new growth balance is formed, which equals the ratio between the distances from the site of the scar to the two ends of the bone, therefore maintaining the relative position of the scar site.. Superstructures can be considered as natural anchoring points for the periosteum into the ossified bone, either due to the insertion of tendons through them into the bone cortex, or by means of steric interference, such as in the tibiofibular junction. This results in a regulatory loop whereby the superstructures determine the tension levels of the two periosteal segments, which control the ratio of growth rates by inhibiting growth plate activity, which in turn maintains the relative position of the superstructure.”