Bone Tissue: Formation & Growth

by Geoffrey Meyer, PhD

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    00:02 I am going to describe bone formation and growth in this lecture. As I pointed out in another lecture in this histology course, there are number of very important functions of bone does and I will repeat them here because when we talk about bone growth and bone formation, the idea is to create bone in the adult can support these different functions such as protecting the heart, lungs and brain, vital organs, forming the skeleton and allowing us to move, supporting the body and body weight. It's also a mineral reserve and I will explain that towards the end of this lecture. It's a reservoir for calcium and phosphate.

    00:55 And I have also given a lecture on bone marrow in this lecture series, in this histology course and there I described the importance of bone marrow and how it is housed within spongy bone and also the medullary components of young bones. At the end of this lecture, I would like you to be able to understand the processes of firstly bone formation, but then the difference between intramembranous ossification and endochondral ossification.

    01:34 I will briefly describe how bone is mineralized to become a very hard structure and then also describe the structure of a synovial joint. So it is important that you understand each of these topics that I have listed on the left-hand side here. On the right hand side, you can see the head of the femur that is going to articulate with the hip bone. And I am going to describe just as an introduction to this lecture, some of the major components of a long bone, of a bone that makes up an axial skeleton, a bone that makes us move by the action of skeletal muscles on it. There are different sorts of bones that I will summarize here. First of all, you can classify bone as being very compact, such as the very firm bone that it is labelled there, on the very edge of this femur, and also it can be spongy or cancellous bone as you see labelled here as well. The spongy and cancellous bone tends to be up towards the epithelial areas of each long bones and that is the area where the bone marrow can be housed as well as in the medullary cavity, which is a central empty space along the diaphysis of a long bone. There are long bones, short bones, flat bones and irregular bones in the body. Think about the bones in our wrist, fingers, the long bone such as the femur one that I have described here, irregular bones again in our wrist joints and in our finger joints, flat bones in our skull, the cranium. So there are different sorts of bones just based on their shape and size as well as being either compact or spongy.

    03:40 In this lecture, I am going to emphasize the diaphysis, the long part of the long bone and also the epiphysis you saw in the previous slide a section cut through the longitudinal axis of these long bones. And I showed you the spongy bone and then in the epiphysial region and also the very compact bone and the medullary cavity that creates the central empty space in the diaphysis of the long bone. And I want you to have a visual image of this bone and take this image through this lecture because what we are going to do in this lecture is go through some of the general simpler processes whereby this long bone develops during fetal life from a cartilage model or a cartilage template. And that is called endochondral ossification. I am going to briefly mention the formation of flat bones such as the bones in the cranium. They develop from a membrane of mesenchyme. No cartilage template precedes the formation of this bone. Therefore, it is called intramembranous ossification.

    05:03 Development of bone or formation of bone purely from a membrane of mesenchyme.

    05:12 I just first of all want to point out the difference between mature bone and immature bone.

    05:20 On the right-hand side, you can see an image, taken through a young person's bone. And I am going to describe the difference between immature bone and mature bone and I'll have a little competition for you to do. As I describe the difference between these two types of bone, I want you to try and identify mature bone on this image and immature bone. I am not going to label it for you. So we are going to have a little competition here, see if you can do it. Well, we often call immature bone, bundle bone or woven bone, and that is because there is no lamella formed as you see in compact mature bone. The lamellae are rings or straight parallel lamellael sheaths of bone matrix laid down by the osteoblasts and then enclosed by osteocytes. They form the osteon in compact bone that are described in our previous lecture.

    06:34 When you see mature bone lying side by side, immature bone as you see here, the immature bone has a different cell concentration. The cells are cluttered close together and there's more of them per unit area. The cells or the osteocytes in mature bone tend to follow straight lines and those lines follow the lamellae formed in the lamella or mature bone. Also, immature bone has a lot more amorphous ground substance in it. So it stains more basophilic as opposed to adult bone or mature bone that is more eosinophilic because it changes its matrix composition. And these changes in staining you see in sections like this, which is stained with normal hemotoxin and eosin. So do you think you can now identify in this section, immature bone and mature bone. I am sure you will identify the dark reddish or bright reddish components being mature bone because you can see the osteocytes lined up, and the more basophilic components of the matrix in the immature bone enable you to make this differentiation.

    08:03 So well done! I want to now just summarize bone cells. If we look at again fetal tissue here, you see some mesenchyme and you will also see some little blastemas or little areas, where bone has started to form. The bone is that purply component you see there and within that purply component in the matrix, you can see little embedded osteocytes.

    08:36 They have been lying down the bone as osteoblasts and when they get surrounded by matrix they then osteocytes.

    08:45 And during their development, they all touch hands with each other. They maintain contact with each other in fine little canaliculi, and that enables nutrition to pass through these little canaliculi to all the osteocytes embedded in matrix. Endosteal cells and periosteal cells are very important components of bone. Endosteal cells are going to line all the small cavities of the bone including all the surface area of that spongy bone I showed at the very start of this lecture. The periosteal cell is going to be on the outside of the bone, the capsule around it. And they are osteogenic. If bone is damaged, those cells can then revert to be osteoblasts and repair the broken bone. Here a mesenchyme cell has developed or differentiate into an osteoprogenitor cell, and it will move to the surface of the bone you can see here and develop into osteoblasts and begin to lay down bone. And we will get back to that in a moment. The osteoblasts in this picture, are those dark stained nuclei cells sitting on the bright clear pink surface of this developing piece of bone.

    10:16 Those osteoblasts have developed from those osteoprogenitor cells I described earlier and they have moved to the surface and they are lying down bone. They have been told to just develop bone from this mesenchymal type origin. You can see the dark pink calcified matrix of the bone. It is still a mature bone, but you can see a very pink little line underneath the osteoblasts. That is called osteoid. It is bone that is yet to be mineralized.

    10:52 So it has a different staining characteristic. But those osteoblasts will gradually mineralize that bone and the osteoblasts will be surrounded by that bone become osteocytes like the one you see here already. Those osteoblasts are secreting collagens type I plus matrix proteins and also vesicles that help with the mineralization process. Here is a lovely picture of an Australian bottlebrush flower. I put it in this lecture to illustrate the structure of a very important component of the matrix and that is the glycoaminoglycan aggregates. They are just like the red components of this bottlebrush flower you see, coming out from a central stem. Just like you see when you look at the molecular structure of these aggregates, these proteoglycan aggregates in the matrix. And those fine little red structures projecting from the central stem with little tiny yellow dots on them, they are the glycoaminoglycans. And they are negatively charged so they can accomodate. They spread out from each other. They repel each other and therefore create large spaces for water. And then allows the matrix, particularly of cartilage, to be very gel like and be very firm and rigid even though it is not calcified or even mineralized. These proteins do a similar thing in bone, they help to embed different components of the matrix and then that matrix becomes highly mineralized. One of the things that happen also is that all these matrix proteins as many of them that maintain a certain array or design of the matrix. You see a picture here of a component of a matrix of a bed, all those steel structures, all those little linked structures represent the way in which certain proteins link all the collagen type I together to form a very strong structure in the bone. And then all the material within that is going to be other matrix components that becomes very mineralized. It gives bone its strength. Here is a section through the osteon or a number of osteons. It is a ground section of bone. You can see osteocytes stained little black structures there embedded in their lacunar space and you can see some very fine black lines. They are the canaliculi, housing processes from these osteocytes. You know bone as well as cartilage, these osteocytes are also involved in mechanotransduction processes. They can feel like on the springs of the mattress I showed you earlier, they can feel different pressures. You know yourself when you are lying on a soft mattress or a hard mattress. It gives you some indication of what the composition of the matrix is. Bone cells do the same thing. They can monitor firmness of the matrix, softness of the matrix and the force that's imposed on that matrix and therefore accordingly adjusts the matrix to be able to withstand those forces and maintain the matrix in a proper chemical and fibrous constitution to actually support the role of being supportive. And just to show you some of the endosteal cells of the very central of the Haversian canal and then you see those look canaliculi that provides nutrients from the endosteal cells in the Haversian canal to all the osteocytes embedded in the matrix.

    15:00 Finally, one important cell is the osteoclast shown in this slide. So at the top of this bony spicules that are being formed, those are macrophages derived cells, they don't come from an osteoprogenitor cell. They are multinucleated. They are large complexes and they eat away bone and they can liberate calcium into the blood. So they are very important in maintaining calcium levels and they are acted on by a couple of hormones that I will describe towards the end of this lecture. They sit in these little spaces called Howship's lacuna and then as I said start to dissolve away all the matrix. Well, that background information on bone, bone structure and the sorts of cells that are in bone and help form bone.

    15:55 Let us now have a look at bone formation. It begins about the eighth week of fetal life.

    16:05 It goes through into the 12th week of fetal life and then a second stage develops around the end of the second trimester. On this section, you can see the two sorts of ways in which bone forms. On the left, there is an image of endochondral ossification. On the right, is an example that was seen before in the previous slide, of intramembranous ossification where the progenitor cells are derived from mesenchyme and they turn into osteoblasts and lay down bone. So they are the two major processes. I am not going to refer to intramembranous ossification in a great deal now for the rest of this lecture because it is involved with formation of bones of the cranium and some of the jaw bones and they simply are derived from this membranous origin. What I am going to concentrate on, is the formation of bone that relates to the long bones or skeletal bones that help us to move our limbs by the action of skeletal muscles on them. So just summarize yourself what do you think are the major components of intramembranous ossification. It is important you understand that process of ossification. Well now look at the other processes. What happens in the fetals, first of all is that mesenchyme cells will develop into chondroblast, cells that lay down cartilage and will secrete type II collagen and also the matrix similar to the matrix that are described a moment ago and also the matrix I described in another lecture in this course on cartilage. And you can see in this image all the little chondrocytes surrounded by matrix. They were chondroblasts that originally derived from the mesenchyme lie down the matrix and now they're surrounded by the matrix. And they are sitting in little spaces called lacuna. You can just see the little dots that represents probably the nuclei of these chondrocytes. But during processing, when there is shrinkage of these chondrocytes these little space you see around in the hilar that we call the lacunar space is really artifact.

    18:46 Those spaces are occupied by the entire cell nucleus and cytoplasm of the chondrocyte. And they can get their nutrition because their matrix allows nutrients to fuse throughout unlike in bone. Well, one of those stages the very first stage of forming a bone is that where the bone is going to be in the body. There is a cartilage model first created and that cartilage model as you see in this slide actually starts to form the rough shape of what the bone is going to be like, not the size of the eventual bone, but it's the shape. And what happens then is a whole series of processes where that cartilage template or model is then replaced by bone through a process I am now going to describe. The cartilage will grow by either interstitial growth meaning the cartilage cells within divide and they spread apart or the cartilage will grow to its proposed shape by appositional growth, which is growth of cartilage on the surface. They are the two ways in which cartilage grow. Well what happens at this stage when at about the second trimester of fetal life, that cartilage model suddenly undergoes some rather drastic changes. For a start, where the diaphysis is going to be. All of a sudden, the perichondrium that is the capsule around the cartilage template, suddenly decides it does not want to be a perichondrium anymore because it is going to turn into a periosteum and start laying down bone. It starts to get a vascular supply so that perichondrium at the future diaphysis changes to be a periosteum and that lays down bone. And you see evidence of that in this section, the very dark purply red material you see there is bone. And it forms a collar and that collar is going to outline the future diaphysis of the bone. The diaphysis of the bone that I described earlier in the lecture, we looked at the mature bone in the femur. And you can see other changes there.

    21:21 You can see a cavity is formed. And within that cavity, there is a lot of cells that represent bone marrow cells. But that is the first stage, a collar and the beginnings of the diaphysis.

    21:39 What happens also is that at a certain region in that cartilage template, the cartilage cells swell up. They accumulate fluid and balloon up and then they cannot get nutrition.

    21:54 So the little areas of matrix between them become calcified. And as that happens, think about at the same time that collar of bone forming in the diaphysis and blood vessels coming in to that periosteum. Those blood vessels bring in osteoprogenitor cells and bone marrow cells. And those osteoprogenitor cells start to form bone and that bone is resolved by osteoclast. And that creates a cavity down the center of the developing bone, down the middle of the diaphysis. It is going to be the eventual cavity of the medullary cavity that we described earlier. So you have got a process now. We have got a bony collar and a zone of hypertrophied cartilage cells that have died and created of bone laid down upon them and then it is being resolved creating that medullary cavity as I have already described.

    23:06 And that is how bone forms originally. And just to summarize this, the area you can see very dark spicules of bone being laid down by lots of osteoblasts there and they are finally resolved away. Endochondral ossification then proceeds further. What I have described results in what we have called a primary ossification center on the bottom left-hand side of destiny? What happens if this cartilage model that is being invaded by osteoprogenitor cells and has had the center taken away by the bone being developed, and then resolved.

    24:01 That hypertrophied area becomes the primary ossification center. And then from the second trimester of fetal life, right and through adulthood, that primary ossification center is going to contribute to the lengthening of the bone until finally at the end of puberty that will seize and the bone length is then determined. So how does the bone grow? Having in a fetus have this primary ossification center, initiating bone growth or bone formation, how does that template that cartilage then grow in length and get to the length of the bone that we see in the mature adult? What happens, just at the beginning of birth or at birth, you get the invasion or the same process occurring up at the epiphysis end of the bone or of the developing bone.

    25:06 Here you see a section. You see the epiphysial cartilage that represents that cartilage component in the previous sections I have showed you whereby there was this hypertrophied zone of cartilage cells and there was absorption away from that down the diaphysis of the bone creating that medullary cavity. By the time, birth has occurred and all the way through now until adulthood, two things happen. You get a secondary ossification center. You can see that to the right of the epiphysial cartilage. That secondary ossification center develops exactly the same way, suddenly the chondrocytes hypertrophy. They die. They become calcified. The matrix is calcified and bone is laid down and then resolved to some significant degree. This area, this secondary ossification center will develop mostly into spongy bone. Remember that spongy bone we saw on the previous section through the femur I showed you towards the start of this lecture.

    26:22 One difference of the secondary ossification center though is that there is no periosteum on the external sides. It remains cartilage because that part of the cartilage and the more distal part of that cartilage is going to be the articular surface of this particular bone. You can see in the far right of this slide another articular surface of articular cartilage. And then what happens is that the bone is going to elongate and widen, but mainly elongate. And it elongates because that epiphysial cartilage component starts to undergo the growth where cartilage cells go through a similar transition through what they did before and bone is being laid down. So just look at those details a little bit more.

    27:25 This summarizes what I described in the previous slide. Down the bottom the question is what reminds is its epithelial cartilage template that is going to be the structure that allows the bone to elongate. And when you look this emphysial plate and you see the processes different zone, on the far right-hand side is cartilage. You can see the cells there are just typical cartilage that results on the reserve cartilage. Then you can see where there's higher concentration of chondrocytes. They have divided. They are proliferating and I call those two zones the reserve zone and the proliferation zone, the running away zone and I will describe why I name that in a moment. Then you've got this zone of hypertrophy of cartilage, the calcification of the matrix and then resorption bone is laid down and then resorbed as I described previously.

    28:35 Now that running away zone that I mentioned is because when the cartilage matrix is calcified and bone is deposited on it and then resorbed to create the diaphysis, the cavity, those two zones reserves in the proliferation run away from that calcified zone. They keep dividing and moving away, getting away from that calcified area consequent in the bone grows in length or the developing bone grows in length. Same thing happens on the other surface, the secondary ossification center. Cells are continually dividing to run away from the zone of calcified matrix. So the bone elongates. It also thickens, gets wider.

    29:26 But bone being laid down form the periosteal collar and then eat their way inside to create a large medullary cavity. The secondary ossification center that I described earlier is mainly occurring not to lengthen the bone, that is done by the epiphysial plate region of proximal to the medullary cavity. The secondary ossification center is mainly to do with the moulding of the shape of the epiphysial head of the bone that I have described again in the start of this lecture and the spongy bone that I showed you. And this shows you some of the processes, little spicules of spongy bone is formed on the cartilage, calcified spicules and is continually removed or remodeled. The bone is red staining here.

    30:24 The cartilage is of very pale stain. You see it here in more detail and it just summarize on the left-hand side some of the processes that I've just described as a review for you.

    30:40 Later on, at the end of puberty, suddenly all those reserve cartilage cells will suddenly start to disappear. And there will be fusion, there will be a closure of this epiphysial plate and there's just a small evidence of the little line going through there in the adult that you can sometimes see. It is called the epiphysial closure. No more growth of the bone occurs. That is all done by this process. The mineralization of bone matrix is rather a complex process. I have just listed here a few of the events that happen and probably the critical event is the first one. For bone to be mineralized, for the osteoblast to release matrix vesicles that they developed inside them, there has to be concentrations of calcium and phosphate far beyond what is normal in other tissues. So initially these osteoblasts secrete osteocalcin and a few other different sorts of proteins and molecules. And that binds calcium in their immediate area and by binding extracellular calcium into that matrix area, the concentration increases.

    32:06 Osteoblasts sense that and they secrete alkaline phosphatase and that increases the concentration of phosphate, which itself starts a big revolving wheel increasing calcium.

    32:23 So the process goes on and on and on until finally those calcium and phosphate levels far exceed threshold and then the osteoblast then release their matrix vesicles by exocytosis and then crystals form. Crystals of hydroxyapatite crystals and the mineralization begins and these crystals then disappear and form right throughout the matrix of the bone.

    32:51 Far more complicated in that but that to summarizes some of the main events.

    32:58 I briefly just want to point out the structure of a synovial joint. We can return to our previous section of this growing bone. I pointed out the two articular surfaces. They are supported on all the way around the joint by a very strong ligament. You can see that ligament in this section. It is the red stained component at the bottom of the slide and also on the top of the image. It is collagen, very dense collagen. The joint cavity is that space between the two articular surfaces. It is full of synovial fluid that is secreted by the synovial organ, very special part of the joint cavity with a very special epithelial cell that secretes that synovial fluid and that synovial fluid gives nutrition to the articular cartilage as I described in a lecture in this course on cartilage and it also acts as a lubricant for the joint. It is a diarthrotic joint. There are different sorts of joints in the body that the anatomists would describe to you. This is a very simple joint that most of us are familiar with, perhaps the knee joint or the hip joint.

    34:19 And finally I just want to mention that bone is a mineral reservoir. Two hormones secreted by the parathyroid and also the thyroid control calcium levels. The parathyroid hormone as is stated there stimulates osteocytes and osteoclasts to reserve bone to take up bone when there is excessive calcium levels in the blood. And conversely calcitonin secreted by the thyroid gland, then inhibits the action and so there is no more calcium being taken up from the bone and therefore calcium levels can be monitored and controlled to be normal.

    35:03 These are very, very very important hormones and again I have discussed these hormones in another lecture in this course on the endocrine system. So, let me now summarize what I have tried to describe in this lecture. The list here is similar to the list I put up at the very start.

    35:23 I want you to be able to know and understand the way in which bone forms, from that basic cartilage model or bone can form purely by mesenchymal cells differentiating to osteoprogenitor cells and then becoming osteoblasts and laying bone down in this membranous component such as we see when bones of the skull are made. There is no cartilage template. The cartilage model that is formed in certain parts of the body corresponds to regions where long bone and other bones are going to develop. It is a part of a skeleton. Part of the skeleton that is involved with movement and the bones have muscles attached to them. Those bones go through endochondral ossification, a process where the bone is formed from a cartilage model.

    36:26 But cartilage undergoes waves of proliferation and then finally they hypertrophy, die, the matrix becomes calcified, bone is laid down on that matrix and resolved or retained or remodeled depending on where the bone is. It could be spongy bone or in the medullary cavity. The bone on the diaphysis is produced by periosteum and I guess it is the form of intramembranous ossification because that periosteum being a membrane just lays down the bony collar, which is going to be compact bone that forms a diaphysis of the bone. And I think it is important to remember that the primary ossification center starts before birth. It starts to lay down the diaphysis and the medullary cavity that creates the zone that is going to develop into the epiphysial plate that is going to be responsible for the elongation of the bone after birth until puberty. And then there is that secondary ossification center remember that is formed, that really is just modeling the epiphysial head of the bone, and mainly it is going to be spongy bone as you see in the diagram to the right. And then I've briefly mentioned the importance of bone in maintaining calcium levels, the action of parathyroid hormone and thyroid hormone. And then finally I've briefly described the structure of a simple synovial joint.

    38:12 So thank you very much for listening to this lecture. I hope you now have some understanding about the way in which bone forms and the way in which bone grows.

    About the Lecture

    The lecture Bone Tissue: Formation & Growth by Geoffrey Meyer, PhD is from the course Bone Tissue. It contains the following chapters:

    • Bone: Formation & growth
    • Immature bone
    • Bone cells
    • Bone formation
    • Bone growth
    • Mineralization of the bone matrix

    Included Quiz Questions

    1. more cellular than mature bone.
    2. stains more eosinophilic than mature bone.
    3. has osteocytes arranged in lamellae.
    4. cancellous bone.
    5. located at the articular surfaces of bone.
    1. lines all the internal surfaces of bone.
    2. lines the outside surface of bone.
    3. is immature bone.
    4. only lines the medullary cavity of mature bone.
    5. cannot repair bone.
    1. intramembranous ossification and endochondral ossification
    2. interstitial growth
    3. intramembranous ossification only
    4. interstitial growth and intramembranous ossification
    5. endochondral ossification only
    1. zone of articular cartilage
    2. zone of proliferation
    3. zone of hypertrophy
    4. zone of calcified cartilage
    5. zone of resorption
    1. Calcium and phosphate ions exceed threshold levels
    2. Calcium ions only exceed threshold levels
    3. phosphate ions only exceed threshold levels
    4. Alkaline phosphatase (AP) is bound to phosphate ions
    5. Alkaline phosphatase (AP) is bound to calcium ions

    Author of lecture Bone Tissue: Formation & Growth

     Geoffrey Meyer, PhD

    Geoffrey Meyer, PhD

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