Ossification | Bone Formation | Histogenesis of Bone | Bone Histology | Embryology of the Skeleton

0:00Hello. Welcome to Byte Size Med. This video is on how bones form and how they grow.

0:08Bones form by a process called ossification. It's also called osteogenesis because it's

0:13forming bone. Now when I studied this, I found it quite confusing. So this video is my best

0:19understanding of ossification. I hope it helps you out. There are three germ layers in an embryo

0:26and they go on to develop all the organs in the body. The ectoderm, the mesoderm and the endoderm.

0:32Bones form from the mesoderm. That mesoderm forms the mesenchyme and the mesenchymal stem cells

0:38can differentiate into different kinds of cells like chondroblasts which can form chondrocytes

0:44and these are cartilage cells. Osteoblasts can form osteocytes and these are bone cells. To

0:51understand ossification, we need to go back a little to some things about cartilage and bone.

0:57Cartilage can be of three kinds. Hyaline, elastic and fibrocartilage. Here we need hyaline cartilage.

1:03It has cells in an extracellular matrix. The cells are chondrocytes, which are located in spaces

1:10called lacunae, either singly or in groups. The matrix consists of collagen, mainly Type II collagen

1:17and a well-hydrated ground substance and these are synthesized by the chondroblasts. Chondroblasts

1:25are located in the perichondrium, which is the connective tissue layer that covers cartilage.

1:32Bone on the other hand has osteoblasts which develop from mesenchymal stem cells called

1:37osteoprogenitor cells. These synthesize the bone matrix which is then calcified.

1:44It has Type I collagen and ground substance, which gets mineralized with the addition of

1:49ions like calcium hydroxyapatite to form the calcified bone matrix.

1:55During this process, some of the osteoblasts get trapped in the matrix and differentiate into

2:00osteocytes, which are also located in spaces. One in each lacuna. Bone also has osteoclasts,

2:08which are multi-nucleated giant cells that resorb bone. They digest the bone matrix.

2:15Osteoblasts form bone, osteocytes maintain it and osteoclasts destroy it. This bone tissue

2:23is distributed in compact and cancellous bone. Compact bone is dense, cancellous bone is spongy

2:30with rods and plates forming trabeculae. Spaces between the trabeculae are filled with bone marrow.

2:37This would be if we took a cross-section of the shaft of a long bone. In long bones, the central

2:43portion of the shaft, that's the diaphysis has a medullary cavity filled with marrow. The ends of

2:49the bone are called the epiphyses. The expanded ends of the diaphysis are called the metaphyses.

2:56The surface of compact bone is covered with connective tissue called the periosteum and

3:01it's got an inner cellular layer, which has those osteoprogenitor cells, osteoblasts and osteoclasts.

3:09The marrow cavities are lined by endosteum which also has these cells.

3:14Now we look at how bone forms. There are two general ways by which ossification can happen.

3:20Intramembranous and Endochondral ossification. In the end, they both form bone. But how they do that

3:27is where they differ. Intramembranous ossification means bone is going to directly form from the

3:34mesenchyme with osteoblasts forming osteoid. This is how most bones of the skull vault and the

3:41facial bones form. They are membrane bones formed by Intramembranous ossification. Endochondral

3:49ossification involves cartilage. It's right there in the name. "Chondral" - cartilage. Here the mesenchyme

3:55forms cartilage first, which serves as a template and that cartilage gets replaced by bone. Cartilage

4:04does not turn into bone, but it gets replaced by bone and we'll see how in a bit. This is how most bones

4:11in the body form, like the long bones. The humerus, the femur, vertebrae, ribs. They are cartilage bones.

4:18They form by Endochondral ossification. First let's look at Intramembranous ossification.

4:25Here like I said before, there is no cartilage template. Bone directly forms from mesenchyme.

4:30The mesenchyme in the area where bone is gonna form condenses. The condensed mesenchyme has stem

4:37cells which differentiate into osteoblasts. That's the bone matrix forming cells. They get to work and

4:44start synthesizing osteoid, which is the matrix before mineralization has happened. Just the

4:50collagen and the ground substance. That matrix then gets calcified. As the osteoblasts form this matrix,

4:57some get trapped forming osteocytes in those lacunae. They have cytoplasmic processes that

5:04sit in canaliculi. This is an ossification centre and multiple ossification centres form and fuse.

5:13The bone matrix organizes into rods and plates forming the trabeculae of

5:18cancellous bone around blood vessels. Between the trabeculae is hematopoietic tissue.

5:24This is marrow. The mesenchyme around that doesn't form bone forms the periosteum

5:31and that lining the marrow cavities forms the endosteum. The bone that first forms in any

5:37process of ossification is immature woven bone. It's irregular and not very strong

5:42and most of it gets remodelled to form lamellar bone.

5:47Underneath the periosteum, compact bone forms and inside that we have cancellous bone. Thus bone has

5:55been formed from the mesenchyme directly. Cartilage was not involved. Endochondral ossification however

6:01is a little longer. Here the mesenchyme first forms chondroblasts, which synthesize the

6:07cartilage matrix, the type 2 collagen and ground substance. The cartilage forms in the shape of the

6:12bone that's going to replace it. This is hyaline cartilage and it has those chondrocytes in lacunae.

6:20It is surrounded by the perichondrium. This is the scaffold for the formation of bone.

6:27Some of the chondrocytes in the centre swell, that's hypertrophy and develop vacuoles. These

6:33chondrocytes compress the matrix and that matrix starts calcifying. Part of the perichondrium near

6:40the middle of the shaft becomes vascularized. That starts changing the perichondrium to the

6:45periosteum, because these cells go from being chondrogenic cells to becoming osteogenic

6:50cells. They form osteoblasts which synthesize the bony matrix. This is a Subperiosteal Bony Collar.

6:59The presence of bone doesn't allow the cartilage cells to get nourishment. The hypertrophied

7:05cartilage cells compress the surrounding cartilage matrix. They synthesize Type X Collagen,

7:10Osteocalcin, Alkaline phosphatase. These hypertrophied cells are thus needed for calcification. The

7:18calcification of the cartilage matrix reduces nutrition to those cells as well. So they die.

7:24That creates spaces in the matrix lined with calcification.

7:29The osteoclasts, that's our bone digesting cells, they form spaces in the bone collar. That allows

7:36the blood vessels along with osteoprogenitor cells and hematopoietic cells to reach the area where

7:42the chondrocytes have died. This is an osteogenic bud and this area in the centre of the diaphysis

7:49is the Primary Centre of Ossification. The osteoprogenitor cells differentiate

7:55into osteoblasts. The osteoblasts start laying down immature cancellous bone. There's a mix of

8:03calcified cartilage and calcified bone. This is the calcified cartilage-calcified bone complex.

8:12The osteoclasts destroy the portions towards the centre forming the medullary cavity, while

8:18the osteoblasts lay down bone around it. So there's remodelling that happens and this

8:23extends towards the epiphysis. Thickening of that bone collar and replacing cartilage with bone.

8:32The epiphyseal ends develop Secondary Centres of Ossification. They form similarly with blood

8:38vessels and those osteoblasts laying down bone, replacing cartilage. The bone that forms in both

8:44cases is osteoid which then gets calcified to form immature woven bone and then remodelled to

8:51form lamellar bone. So there is a Primary Centre of Ossification in the diaphysis and Secondary

8:57Centres in the epiphysis. They are separated by a plate of cartilage called the Epiphyseal Growth

9:04Plate. The surface of the epiphyses have articular cartilage because they articulate with other bones

9:10forming joints. These are the only two sites where cartilage remains. The articular cartilage

9:16stays for life. But the growth plate, that is responsible for the longitudinal growth of bones.

9:24But now we've formed bone by Endochondral Ossification and longitudinal growth of bone also happens by

9:31Endochondral Ossification. Bone is going to replace cartilage from the diaphyseal end

9:37of that growth plate. The growth plate thus can be divided into zones, histological zones. It's

9:44similar to how this process just happened. Bone is going to replace cartilage. So there's a Zone

9:50of Reserve Cartilage towards the epiphyseal end. That's just typical hyaline cartilage with random

9:55chondrocytes. It attaches the growth plate to the epiphysis. Then there's the Zone of Proliferation.

10:01That's where the chondrocytes undergo mitosis. They proliferate and line themselves up along the

10:07long axis in parallel rows. Then we have the Zone of Maturation and Hypertrophy. The chondrocytes

10:13get larger in size. Then they calcify the matrix. That's the Zone of Cartilage Calcification, where

10:19the chondrocytes go to die. From the diaphyseal end, we have the zone of ossification where along

10:25with capillaries, the osteoprogenitor cells enter and form osteoblasts. The osteoblasts can

10:32then form bone matrix on that calcified cartilage, ultimately forming bone from the diaphyseal end.

10:38But since the cartilage is both proliferating at one end and dying at the other, the rates are

10:45almost the same. So the thickness of the plate doesn't change. The bone just keeps pushing it

10:49upwards as it grows, increasing the length of the diaphysis and thus bone grows longitudinally. Once

10:58that bone has reached its final length, by then the cartilage stops proliferating. Thus destruction

11:04is more and bone replaces cartilage leaving behind that growth plate as an epiphyseal line.

11:13The Primary and Secondary Centres of Ossification have fused. Now bone can no longer grow.

11:20That's longitudinal growth. But bone also grows radially. Now that's not Endochondral

11:25Ossification. It's from the periosteum, the outer covering of bone. The endosteum lines the marrow

11:32cavities. But to make it easier, I'll just draw it as the inner lining. The centre of the diaphysis

11:37has the medullary cavity. These layers have cells. The osteoblasts in the periosteum deposit bone.

11:44That's Subperiosteal Intramembranous Ossification, while the osteoclasts in the endosteum digest bone.

11:52Both these processes balance such that bone does increase in thickness, while the medullary

11:58cavity increases in size as well. So we've got Intramembranous ossification without a cartilage

12:05template and endochondral ossification with the cartilage template. And that's how bone develops

12:11and grows. That's the process of ossification. I hope this video was helpful. If it was you can

12:16give it a like and subscribe to my channel. Thanks for watching and I'll see you in the next one!:)