Anatomy I: Bone Development

osteocalcium

What requires vitamin K to function?

- vascular

- innervated

- with lymph vessels

- surrounded by the periosteum (irregular dense CT)

What are the characteristics of bone tissue?

Internal surface

Where is the endosteum found?

External surface

Where is the periosteum found?

- osteocytes

- matrix: 50% mineral salts; 25% proteins (collagen type I); 25% water

What is the composition of bone tissue?

Bone

What is the blue sticker pointing to?

Periosteum

What is the pink sticker pointing to?

Bone marrow

What is the yellow sticker pointing to?

A mesenchymal stem cell line

What cell line do osteoprogenitor cells come from?

We know it is a trabeculae (spongy) because it lacks a Haversian canal

Is this a section of a spongy or compact bone?

Osteoid and calcium hydroxyapatite

What is bone matrix composed of?

Unmineralized matrix composed of type I collagen and glycosaminoglycans (GAGs)

What is osteoid?

calcium hydroxyapatite

What part of the bone gives bone its strength and rigidity?

Collagenous mesenchymal

Bone development begins with the replacement of ____________ ____________ tissue by bone

Woven

The first type of bone formed is called _______ bone and is characterized by having the collagen fibers randomly organized

Lamellar

Woven bone is later replaced by ___________ bone, which has a parallel ring of collagen

Woven

*irregular mesh of collagen

What type of bone is this?

Lamellar

*highly organized collagen

What type of bone is this?

Collagen fibers are organized like a "mesh"; irregular organized pattern. Less mineral than mature bone.

How are collagen fibers organized in immature, or woven bone?

Osteons

Woven bone does not have _________.

T

T or F woven bone is restricted in size

intramembranous ossification

What type of bone formation goes directly from embryonic connective tissue or mesenchyme into bone?

endochondral ossification

What type of bone formation goes from mesenchyme into cartilage, then into bone?

endochondral ossificiation

What type of bone development do long bones, such as the femur, go through?

1. Mesenchyme becomes highly vascularized; mesenchymal cells aggregate.

2. Mesenchymal cells differentiate into osteoblasts that begin to produce osteoid, this is called a bone blastema. Osteocytes become interconnected, forming a functional syncytium. Osteoblasts line the surface of the bone blastema.

3. Calcium is transported by blood vessels, which initiates the mineralization process. (Using collagen for guidance)

What are the steps of intramembranous ossification?

Osteoblasts

_________ line the surface of the bone blastema in the second step of intramembranous ossification

first step of intramembranous ossification

If we see a group of mesenchymal cells means what?

Mineralization process

In the third step of intramembranous ossification, calcium is transported by blood vessels, which initiates what?

Committed cartilage (mesenchymal cells)

Endochondral ossification; growth in length: what is 1

Compact nodules

Endochondral ossification; growth in length: what is 2

Proliferating chondrocytes

Endochondral ossification; growth in length: what is 3

hypertrophic chondrocytes

Endochondral ossification; growth in length: what is 4

Osteoblasts (bone)

Endochondral ossification; growth in length: what is 5

Blood vessel

Endochondral ossification; growth in length: what is 6

Proliferating chondrocytes

Endochondral ossification; growth in length: what is 7

Epiphyseal growth plate

Endochondral ossification; growth in length: what is 8 and 11

Bone marrow

Endochondral ossification; growth in length: what is 9

Bone

Endochondral ossification; growth in length: what is 10

secondary ossification center

Endochondral ossification; growth in length: what is 12

Normal cartilage (individual cells)

What is 1

Cell proliferation (growth here)

What is 2

Hypertrophic individual cells

What is 3

Areas of bone marrow

What is 4

Compact bone area

What is 5

hypertrophic cells

What is 6

Cartilage

What is 7

Type II collagen

What type of collagen is in the matrix of cartilage?

Type I collagen

What type of collagen is in bone?

(1) WNT pathway to repress chondrocytic differentiation instead of becoming cartilage

(2) the transcription factor Runx2, and differentiate into osteoblasts

- in a later stage, these Runx2 - positive cells express osterix and then become osteocytes

What are the molecular features of membranous ossification?

Osterix

Runx2-positive cells express _______ and then become osteocytes

epiphyseal cartilage

Which zone of endochondral ossification is 1?

Reserve zone

Which zone of endochondral ossification is 2?

Proliferative zone

Which zone of endochondral ossification is 3?

Hypertrophic zone

Which zone of endochondral ossification is 4?

vascular invasion zone

Which zone of endochondral ossification is 5?

Reserve zone

What zone is the blue sticker?

Proliferative zone

What zone is the pink sticker?

Hypertrophic zone

What zone is the green sticker?

Vascular invasion zone

What zone is the yellow sticker?

Blood vessels

What is required to form bone?

Bone grows from hypertrophic zone towards proliferative zone

"Running away"

What is the direction of bone growth in regard to the proliferation zone?

Ossification-osteoclast front

The____________ invades and replaces chondrocytes as it moves past the site previously occupied by hypertrophic chondrocytes

Epiphyseal cartilage

What is 2

Secondary growth plate

What is 3

Perichondrium

What is 4

Primary growth plate

What is 5

zone of provisional calcification (ZPC)

What is 6

Primary metaphyseal spongiosa

What is 7

Metaphysis

What is 8

Reserve zone

Which zone is the light blue sticker

Proliferative zone

Which zone is the pink sticker

Hypertrophic zone

Which zone is the green sticker

Vascular invasion zone

Which zone is the yellow sticker

Diameter

In appositional growth, bone increases in _________.

Endosteal, Periosteal

In appositional bone growth, the bone is absorbed on the _________ surface and added to the _________ surface

A mutation in the FGFR3 (fibroblasts growth factor receptor 3) gene, which plays a role in the formation of collagen and contributes to the ossification of bone. This mutation prevents adequate bone formation in utero, resulting in a shortened stature and a large head

Clinical correlation: What is achondroplasia due to?

Cartilage

Identify the tissues and growth zones: yellow sticker

Beginning of bone formation

Identify the tissues and growth zones: blue sticker

Mature bone

Identify the tissues and growth zones: pink sticker

This is in the hypertrophic zone; collagen type 10 is only made in this zone (collagen type X)

The unique type of collagen found in the yellow circled area is.....

1. Mesoderm-derived mesenchymal cells differentiate into chondrocytes.

2. Chondrocytes proliferate rapidly and secrete extracellular matrix to form a hyaline cartilage model

3. Chondrocytes near the center of the model begin to undergo hypertrophy and alter the matrix they produce, which allows calcification

4. Calcification prevents nutrients from reaching the chondrocytes, so they die

5. Blood vessels invade the space left by dead chondrocytes, and the blood vessels bring osteogenic cells and trigger the transformation of the perichondrium into periosteum

6. Osteoblasts of the periosteum form a collar of compact bone on the surface, forming the ossification center

What are the steps of endochondral ossification?

1. Mesoderm-derived mesenchymal cells express the transcription factor Sox9, which leads to proliferation and differentiation into chondrocytes

2. An increase is reactive oxygen species (ROS) leads to chondrocyte hypertrophy, the cells start secreting collagen type 10, and increase the secretion of fibronectin. They also secrete VEGF and attract macrophages, which will degrade the matrix once the chondrocyte die

3. Osteoprogenitor cells carried by blood vessels express Runx2 and differentiate into osteoblasts

4. Runx2-positive cells express osterix and become osteocytes

What are the molecular features of endocondral ossification?