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MSK > Bone development > Flashcards

Bone development Flashcards

1
Q

Where does bone tissue originate from?

A

Mesodermal (mesenchymal) germ layer

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2
Q

What two types of mesodermal germ layers exist?

A

Lateral plate mesoderm

Paraxial mesoderm

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3
Q

What bones does the lateral plate mesoderm give rise to?

A

Limb and long bones

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4
Q

What skeleton does the lateral plate mesoderm give rise to?

A

Appendicular skeleton

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5
Q

What skeleton does the paraxial mesoderm give rise to?

A

Axial skeleton

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6
Q

What are the three distinct lineages that generate the skeleton?

A

Somites - axial skeleton

Lateral plate mesoderm - limb skeleton

Cranial neural crest - branchial arch and craniofacial bones and cartialge

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7
Q

What skeleton do the somites form?

A

Axial skeleton

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8
Q

What skeleton does the lateral plate mesoderm form?

A

Limb skeleton

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9
Q

What skeleton does the cranial neural crest form?

A

Branchial arch and craniofacial bones

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10
Q

What are the two major modes of bone formation?

A

Intramembranous ossification

Endochondral ossification - long bones

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11
Q

What do endochondral ossification and intramembranous ossification have in common?

A

They both involve the transformation of a preexisting mesenchymal tissue into bone tissue

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12
Q

What does intramembranous ossification entail?

A

Direct conversion of mesenchymal tissue into bone

Characteristic way in which flat bones of the skull are formed

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13
Q

Steps of intramembranous ossification

A

Neural crest-derived mesenchymal cells proliferate and condense into compact nodules

Some of these cells develop into capillaries and some become osteoblasts

Osteoblasts secrete osteoid matrix

The osteoid matrix becomes calcified

Osteoblasts are separated from the region of calcification by the matrix they secrete

Ocassionally they become trapped in the calcified matrix and become osteocytes

Calcification proceeds and bony spicules radiate out from the region where ossification began

The entire region of calcified spicules becomes surrounded by mesenchymal cells that form the periosteum

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14
Q

What is the osteoid matrix composed of?

A

Collagen-proteoglycan matrix

Can bind calcium salts

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15
Q

What cells compose the periosteum that surround the bone?

A

Cells on the inner surface of the periosteum become osteobladts and deposit osteoid matrix

Many layers of bone are formed

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16
Q

What are important factors in intreamembranous ossification?

A

BMPs

CBFA1 transcription factors

17
Q

What are BMPs?

A

Bone morphogenetic proteins

Released by head epidermis

Instruct the neural crest-derived mesenchymal cells to become osteoblasts

By activating CBFA1 gene in mesenchymal cells

Also activate genes for osteocalcin, osteopontin and other bone-specific ECM proteins

18
Q

What happened to mice lacking the CBFA1 gene?

A

Died shortly after birth

Showed skeletal defects

Skeletons lacked bone

19
Q

What happened to mice with heterozygous CBFA1?

A

Stunted growth

Clavicle - absent or deformed

Skull sutures fail to close

20
Q

What does endochondral ossification entail?

A

Formation of cartilage tissue from aggregated mesenchymal cells

Subsequent replacement of the HYALINE cartilage by bone

21
Q

What are the 5 processes of Endochondral ossification?

A

Bone collar formation

Cavitation

Periosteal bud invasion

Diaphysis elongation

Epiphiseal ossification

Boys cant pee during erections

22
Q

Describe the process of bone collar formation

A

Primary ossification center develops in the center of the hyaline cartilage

This is the source of bone formation

Mesenchymal cells in the perichondrium differentiate int osteoblasts

Start to secrete osteoid against the diaphysis

The hyaline cartilage diaphysis is now encased in compact bone

This bone collar gives developing bone structural support to begin hardening

23
Q

Describe the process of cavitation

A

Chondrocytes stop dividing and instead increase in size dramatically - hypertrophy

Hypertrophic condrocytes secrete membrane-bound vesicles into the ECM containing enzymes active in the generation of calcium and phosphate ions

This hardening is called calcification - happens from the center

Calcified hyaline cartilage is now impermeable to diffusion of nutrients

Since the chondrocytes can’t receive any nutrients -> begin to die

When they die they leave small cavities -> allow for blood vessels to travel through

24
Q

Describe the process of periosteal bud invasion

A

The dying chondrocytes signal to the body about their anaerobic environment

Previously nutrients were deliveres through cartilage through simple diffusion

The periosteal region is invaded by a bud containing blood vessels and nerves

Allows nutrients and oxygen to enter the cavities previously inhabited by chondrocytes

Osteoblasts and osteoclasts take advantage of this highway into the bone and enter the bone along with nutrients

The osteoblasts secrete osteoid into the remaining hyaline cartilage -> gives rise to early spongy bone

25
Q

Describe the process of diaphysis elongation

A

After the nutrient source is delivered to the center of the bone, the diaphysis region has the resources to elongate

Elongated region is powered by cells dividing in the primary center of ossification

Elongated region = medullary cavity - where bone marrow is contained

26
Q

Descrive the process of epiphyseal ossification

A

Just before birth - epiphysis will develop own centers of ossification

As they can’t remain made of cartilage -> structurally weak

These are secondary centers of ossification

27
Q

What are secondary centers of ossification?

A

Centers of ossification that develop in the epiphysis just before birth to allow the hyaline cartilage to develop into bone

28
Q

Why do we need secondary centers of ossification? Why can’t bones grow completely from the center?

A

Region between the primary and secondary centers of ossification = epiphyseal plate

AKA growth plate

Remaining cartilage from hyaline model

How bones grow as we age

As long as the epiphyseal growth plates are able to produce chondrocytes, the bone continues to grow

29
Q

What acts as a model for the bone that is formed?

A

Hyaline cartilage

30
Q

Describe the process by which hyaline cartilage is formed

A

Mesenchymal stem cells comit to become chondrocytes

The commited mesenchyme cells condense into compact nodules and differentiate into chondrocytes

31
Q

What causes the mesenchymal cells to become chondrocytes?

A

Paracrine factors

Causes the mesenchymal cells to express Pax1 and Scleraxis

Transcription factors

Activate cartilage-specific genes

32
Q

What initiates the condensation of chondrocytes to form nodules?

A

N-cadherins

N-CAM

SOX9 gene - expressed in pre-cartilagenous condensations

MSK (22 decks)

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