Bone Cells | Bone Physiology | Bone Remodelling | Structure of Bone | Human Histology

0:00Hello. Welcome to Byte Size Med. This video is on the different

0:03cells of Bone Tissue and how they work together.

0:09Bone tissue is connective tissue, a specialized connective tissue. Let's go back a little and

0:15look at the general structure of connective tissue. It's got cells and an extracellular

0:20matrix which includes protein fibres like collagen and elastin and ground substance.

0:27The ground substance includes glycosaminoglycans, proteoglycans and adhesive glycoproteins.

0:33Now what these actually are depends on the type of connective tissue. But in connective tissue

0:40proper which is your general connective tissue, the main resident cells are fibroblasts and fibrocytes.

0:48Fibroblasts come from mesenchymal stem cells. Fibroblasts are the ones that synthesize all

0:53this matrix stuff. Fibrocytes are a less active version of fibroblasts.

0:59Some cells like monocytes can migrate into connective tissue if they've got some work to do.

1:05Bone is specialized connective tissue. It's supportive. It's special because

1:10this extracellular matrix is calcified, meaning it's got these kinds of organic

1:15components but also inorganic stuff. Predominantly Calcium Hydroxyapatite.

1:23The cells of bone are osteoblasts and osteocytes. The stem cells that can form these osteoblasts are

1:30osteoprogenitor cells or osteogenic cells. The fourth type of cell is an osteoclast and it's

1:37derived from monocytes, possibly by the fusion of monocytes. Those are the four main types of

1:43cells in bone tissue and now we're going to look at what they all do and how they work together.

1:50The osteoprogenitor cells or the osteogenic cells are derived from the mesenchyme. They

1:56are stem cells, so they can differentiate into other cells and here that will be the

2:01osteoblast. If you look at the shaft or the diaphysis of a long bone, they usually have

2:06a medullary cavity with the cancellous bone around them. The trabeculae of the

2:11cancellous bone are lined by endosteum. It lines all the marrow spaces. Around the

2:17cancellous bone is compact bone and the outer layer is periosteum. This endosteum

2:23and periosteum, they have cellular layers where these osteogenic cells reside and when needed

2:29they can differentiate into osteoblasts. So they are important for bone growth and repair.

2:37Osteoblasts are the fibroblast equivalent in bone tissue. They can synthesize all the extracellular

2:44matrix proteins. What do they form? The protein fibres are like collagen. Bone has predominantly

2:51Type I collagen. It's got the one in it. That's how you remember it. Bone has Type "One" collagen.

2:57Adhesive glycoproteins like Osteocalcin and Osteonectin,

3:01which bind avidly to calcium and are thus important for bone mineralization.

3:07This matrix that's synthesized by osteoblasts is called osteoid. Its bone matrix with the

3:13protein components, but it's not calcified yet. That osteoid undergoes mineralization, where inorganic

3:21components like Calcium Hydroxyapatite get added to it and that forms the calcified bone matrix.

3:29The bone matrix has both organic and inorganic components. The organic part of the bone matrix

3:36gives it tensile strength. The inorganic part gives it compressional strength. So they're both

3:42important for bone strength. Osteoblasts are the ones that synthesize all the proteins for

3:48the extracellular matrix. That's basically the osteoid. So osteoblasts synthesize the osteoid.

3:55This process of mineralization is also regulated by the osteoblasts. Osteoblasts

4:01also produce cytokines like the Macrophage - Colony Stimulating Factor and the Receptor

4:07for the Activation of Nuclear factor Kappa B ligand. Now this stuff sounds like gibberish

4:13for now, but we will come back here. Osteoblasts are clearly very active cells and as such these

4:20cuboidal cells have got lots of rough endoplasmic reticulum and a well-defined Golgi apparatus.

4:26Some of the osteoblasts undergo apoptosis once their job is done. Some remain as bone

4:32lining cells. But while they synthesize the osteoid, some of them get trapped in that

4:38newly forming matrix. They differentiate and these cells are now called osteocytes.

4:46So osteocytes are more mature cells and they're not very active. They have lesser

4:50rough endoplasmic reticulum and Golgi apparatus. They sit inside lacunae which are spaces in the

4:56bone matrix that houses these cells. They have cytoplasmic extensions that are in the spaces

5:03called canaliculi. Mature bone is lamellated. It's got layers and layers of matrix and these cells

5:11sit in those lacunae, trapped between the layers with those cytoplasmic processes inside canaliculi.

5:19Between the cells, we have the calcified bone matrix which isn't going to allow diffusion.

5:24But the canaliculi have some extracellular fluid and that allows exchange to happen

5:29with the cells. The cytoplasmic processes have Gap Junctions, which helps connect the cells

5:35so that they can communicate. Osteoblasts have Gap Junctions too. Ions like calcium can move

5:41between the cells through these Gap Junctions and this forms the osteocytic membrane system.

5:49Together the cells in the system work like a mechanosensor sensing the load on

5:53the bone and deciding what to do next. Osteoblast synthesize bone matrix and osteocytes maintain it.

6:02Osteoprogenitor cells can form these osteoblasts when required.

6:08Bone in the body is very much alive. It's a dynamic structure and as such

6:13both synthesis and resorption of bone happens. Synthesis of bone matrix is by

6:20the osteoblasts. Resorption of the bone matrix, which would be destroying it Is by osteoclasts.

6:29The fourth type of cell is the osteoclast. The osteoclasts are derived from monocytes,

6:34possibly by the fusion of monocytes. So they are multi-nucleated giant cells.

6:41There are different kinds of giant cells that you'll come across while studying physiology

6:45and pathology. Some of them are physiological, most of them are actually pathological. The

6:51osteoclast however, is a good example for a physiological giant cell. The fact that

6:57it comes from the monocyte-macrophage system makes sense, because its job is to resorb bone.

7:03Osteoclasts are regulated by osteoblasts. Remember those cytokines that osteoblasts

7:08produce? They guide formation and proliferation of osteoclasts. Macrophage-CSF, the RANK Ligand.

7:16They bind to the osteoclast precursor cells and would increase mature osteoclast formation.

7:23The RANK Ligand would bind to the RANK Receptor on the osteoclast precursor cells.

7:29Another cytokine is Osteoprotegerin. Now this binds to the same receptor and stops the RANK

7:35Ligand from binding to those cells and thus would inhibit pre-osteoclasts from becoming

7:40mature osteoclasts. It's thus also called the Osteoclastogenesis Inhibitory Factor.

7:49And what happens once the osteoclast is active? It has a ruffled border where it makes contact

7:54with the bone, forming a circumferential seal. The attachment is mediated by adhesive glycoproteins.

8:01The integrins on the osteoclast bind to vitronectin on the surface of bone.

8:07The space beneath that border forms the Subosteoclastic Zone, because it's beneath the

8:12osteoclast. The depression it creates as it digests bone becomes larger and larger.

8:19This depression where the osteoclast sits is called the Howship Lacuna or the Resorption Bay.

8:26It's got lots of nuclei and other organelles in the Basal Zone.

8:31It has a Clear Zone with actin filaments on the sides of the ruffled border and the Vesicular

8:38Zone with lysosomes and vesicles with enzymes meant to digest bone. Remember that bone matrix

8:45is organic and inorganic. The organic part has proteins like collagen fibres and the inorganic

8:51part has minerals like Calcium Hydroxyapatite. The osteoclast has Carbonic anhydrase. Carbon dioxide

8:59combines with water and with this enzyme, it forms carbonic acid. A familiar reaction in physiology.

9:07That then forms bicarbonate and hydrogen ions. Bicarbonate leaves the cell in exchange for

9:13chloride. But what happens to the hydrogen ions? The hydrogen ions are pumped into the Subosteoclastic

9:20Zone by a Hydrogen ATPase pump, where it creates an acidic environment breaking down Calcium

9:27Hydroxyapatite. The calcium and phosphate ions are then released into the bloodstream.

9:33So bone resorption increases the plasma calcium levels by taking calcium out of the bone.

9:40If we take an example of the parathyroid hormone, which is important for calcium regulation in the

9:46body, it causes bone resorption which would be by the osteoclasts. But those cells don't

9:52have a receptor for this hormone. The osteoblast has a receptor for the parathyroid hormone. That

10:00increases the release of cytokines, which bind to the osteoclast precursor cells and convert them

10:05to mature osteoclasts. They resorb bone, releasing calcium and increasing the calcium levels in blood.

10:13That's how the parathyroid hormone can use bone resorption to restore blood calcium levels when

10:18they're low. But bone also has those organic components like collagen and ground substance.

10:24The osteoclast vesicles have enzymes like acid phosphatase acid hydrolases, Matrix

10:31Metallooproteinases like collagenase, which digest those organic components when they're

10:36released. Again into that Subosteoclastic Zone. The osteoclast has now absorbed bone.

10:45Osteoblasts and osteoclasts work together and that helps bones change shape, grow and repair. Bones can

10:52grow longitudinally, but also radially. If we ignore longitudinal growth for now, bones increase in girth,

11:00so radially, by appositional growth. If this is the medullary cavity, surrounded by cancellous bone, the

11:07marrow spaces are all lined by endosteum. But to make it simpler, I'm just going to draw it as the

11:12inner lining of bone. It's got cells. The cell we need for this is the osteoclast. The bone digester.

11:20Around cancellous bone is compact bone and then the periosteum. Again it has cells. What we need now

11:28are the osteoblasts. As the osteoblasts lay down new bone, the osteoclasts resorb bone from the

11:36centre. Increasing the thickness of the diaphysis while increasing the size of the medullary cavity.

11:43That's how bones undergo modeling. That's bone modeling, but throughout life bones

11:51undergo remodeling in response to the different stresses and strains that they're subject to. Bone

11:56gets destroyed, bone gets formed. This again involves the balance between the osteoblasts

12:02and the osteoclasts. There are five key steps in a remodeling cycle. The first is activation,

12:09where osteoclast precursors are recruited and then activated. What do they do? Resorb bone.

12:17So that's the next step, bone resorption. Then those osteoclasts undergo apoptosis. We don't need them

12:23anymore. The next step is reversal. Now we move from resorbing bone to forming bone. The cell we need

12:31for that is the osteoblast. Osteoblasts then do the next step of bone formation, which includes osteoid

12:39formation and then mineralization of the bone matrix. During that process, some of the osteoblasts

12:46get trapped and differentiate into osteocytes. Once mineralization is done, we've reached the

12:52final step of termination, where osteoblasts which haven't gotten trapped either undergo apoptosis or

12:59they remain as bone lining cells. That is how bones undergo remodeling. By using all those bone cells.

13:09So the osteogenic cells are The Creators, the osteoblasts are The Builders,

13:16The osteoclasts are The Destroyers and the osteocytes are The Prisoners. Those are the

13:23cells of bone tissue and they work together. I do hope this video was helpful. If it was, you can give

13:29it a like and subscribe to my channel. Thanks for watching and I'll see you in the next one!:)