Development of Skeletal Tissue

Question 1

What is the skeletal muscle developmental precursor?

Answer 1

Paraxial Mesoderm

Question 2

How does embryonic connective tissue differ from mature connective tissue?

Answer 2

Embryonic: Cells are mesenchymal, high ratio of cells to ECM, ECM includes fibrous proteins embedded within hydrated, amorphous ground substance

Mature: high ratio of ECM to CT cells, consits of loose and dense fibrous CT, bone, cartilage as well as blood and lymph

Question 3

What is the STFM? And what does it originate from?

Answer 3

Skeletal tissue forming mesenchyme (STFM)

Originates from Scleratome tissue of somites (paraxial mesoderm) and somatic mesoderm (lateral mesoderm)

Question 4

What promotes mesenchyme to epithelial transformation? What cells do this?

Answer 4

N-cadherin

Preskeletal condensation: epithelial-like cells of the STFM

Question 5

What specific transcription factor is expressed to turn preskeletal mesenchyme into cartilage? Into bone?

Answer 5

Cartilage –> Sox-9

Bone –> Runx-2 (Cbfa-1)

Question 6

What does Sox-9 do?

Answer 6

Causes preskeletal condensation to differentiate into chondroblasts and to secrete Type II collagen

Question 7

Name the four main steps in carilage formation.

Answer 7

1. Preskeletal condensation
2. Central cells differentiate into chondroblasts
3. Chondroblasts begin to secrete carilage matrix
4. Carilage element forms; the surrounding cells form a perichondrium (fibrous capsule)

Question 8

What is intramembranous ossification?

Answer 8

When bones form directly from a preskeletal condensation that resembles a membrane of mesenchymal cells.

Question 9

What transcription factors aid in intramembranous ossification?

Answer 9

STFM cells exposed to low levels of BMP causing them to express Runx-2 which turns them into osteoblasts

Question 10

What types of bone are usually formed by intramembranous ossification?

Answer 10

Superficial bones – Flat bones

Question 11

What is endochondral ossification?

Answer 11

Cells in STFM condensation form a carilage model of the bone.

Question 12

What signaling molecules induce endochondral ossification?

Answer 12

Indian Hedgehog (Ihh) and sometimes Runx-2 – chondrocytes undergo hypertrophy and secrete type X collagen and bone specific proteins

VEGF also secreted – which stimulated blood vessel ingrowth that is accompanied by invasion of osteoblasts

Question 13

What does endochondral ossification allow for?

Answer 13

Allows bones to grow in length d/t the presence of a cartilage growth plate (Epiphyseal plate) at one or both ends of forming bone

Question 14

What are ossification centers and what are they a good measure of?

Answer 14

Areas of a bone primordia in which the ossification process begins

Clinically important for estabilishment of bone age – useful index of skeletal growth and maturation, amount of epiphyseal cartilage retained within the skeleton

Question 15

What are primary ossification centers?

Answer 15

The inital ossification center to form in a developing bone.

Question 16

Where are primary ossification centers located in long bones? In flat bones?

Answer 16

In long bones they are usually in the shaft region

In flat bones they are usually in the center of the bone primordia

Question 17

What are secondary ossification centers?

Answer 17

Additional centers of bone formation appearing in the prenatal, postnatal or postpuberal period.

Question 18

Where are secondary ossification centers commonly located?

Answer 18

At the ends of long bones, the heads of ribs, the surfaces of vertebrae.

Question 19

In long bones, what does closure of secondary ossification centers result in?

Answer 19

Disappearance of the epiphyseal plate

Question 20

What is the difference between a pituitary dwarf and a achondroplastic dwarf?

Answer 20

Pituitary dwarf = cretinism, caused by hypothyroidism, experience mental retardation as well as skeletal and ear anomalies, bone age is younger than it should be for chonological age

Achondroplastic dwarf = autosomal dominant, assoc with mutation of Fibroblast Growth Receptor 3 (FGFR-3) interference with epiphyseal plate development results in diproportionally shortened limbs but normal sized trunk, have short fingers and accentuated lordosis, normal intelligence

Question 21

How is gigantism different from acromegaly?

Answer 21

Depends on when hyperpituitarism occurs – hyperpituitarism causes overproduction of growth hormone

If it occurs before epiphyseal plate closure –> gigantism

If it occurs after epiphyseal plate closure –> acromegaly (disproportionate enlargement of face, hands and feet)

Question 22

How does Marfan’s affect skeletal development?

Answer 22

Defect of production of fibrillin, a component of ECM

Autosomal dominant

Individuals have spider-like elongated digits, aortic aneurysms, eye and spine abnormalities and joint hypermobility

Question 23

How does mucopolysaccharidoses affect skeletal development?

Answer 23

Metabolic disease, affects bone formation resulting in dwarfism and bone irregularities

Autosomal recessive

Absence or defect in enzyme causes accumulation of glycosaminoglycans in tissues and cells

Chronic, progressive distortinos of face and skull, thickened hairy skin, organ enlargement, altered mental devo

Question 24

How does osteogenesis imperfecta?

Answer 24

Caused by defect in expression of Type I collagen gene

Dominant inheritance

Affects skeleton, eyes, ears, joints, spine and teeth