Development of the Musculoskeletal system

Question 1

Musculoskeletal system

Answer 1

Consists of bones, cartilage, muscles, ligaments, tendons

Functions:
Support the body, provision of motion, protection of vital organs (brain, viscera), main storage system for calcium and phosphorus

Question 2

Blastocyst Formation

Answer 2

Blastocyst is a single-layered hollow sphere of cells that forms from the zygote through cleavage process

Question 3

Blastocyst layers

Answer 3

1. Epiblast (outside layer)- becomes ectoderm
2. Hypoblast (inner layer)- becomes the endoderm
3. Cells between the epiblast and hypoblast form the Mesoderm

Question 4

Gastrulation

Answer 4

Stage in embryonic development where the blastocyst is reorganized into a multilayered structure called the gastrula

Formation of 3 germ layers

Initiated at primitive streak

Question 5

Gastrula layers (germ layers)

Answer 5

• ectoderm
• mesoderm
• endoderm

Question 6

Stages of further development of gastrula

Answer 6

• Ectoderm will pinch inside creating a neural tube
• Neural tube separates the mesoderm into 2 paraxial mesoderms on either side. Paraxial mesoderm differentiates into the somites
• The mesoderm directly beneath the neural tube becomes the notochord
• The lateral mesoderm becomes the limbs
• Neural crest cells form from the corners of the neural tube folding of ectoderm. They detach and become other cells, many PNS nerves.

Question 7

Somitogenesis

Answer 7

Each somite differentiates into 3 components

1. Scleratome (differentiate into cartilage, vertebrae and ribs)

Dermamyotome: 2. Dermatome (dermis) and 3. Myotome (muscle)

Question 8

Osteogenesis

Answer 8

Requires mesenchyme cells

Mesenchyme from scleratomal part of somites- Give rise to segmented axial column (vertebral column, ribs, sternum)

Mesenchyme of lateral plate mesoderm- gives rise to appendicular skeleton (limbs and respective girdles)

Mesenchyme derived from ectodermal neural crest- gives rise to facial bones and bones that cover the brain

Question 9

Types of bone (gross observation)

Answer 9

Viewed as a gross observation or microscopic observation

A more gross observation of bone (eg. Cross section)
- Compact bone= Dense areas of bone without cavities (80% of mass)
- Cancellous or spongy bone= Areas of bone (struts and rods) with interconnecting cavities (20% of mass)

Question 10

Types of bone (microscopic view)

Answer 10

Viewed as a gross observation or microscopic observation

Two types of organization
1. Woven bone or immature bone
- First to appear during development
- Randomly arranged matrix components (Eg. Cells, collagen)

2. Lamellar bone or mature bone
   - In adults
   - Discrete sheets or layers of matrix

Question 11

Histological differences in bone types

Answer 11

No histological differences

Question 12

Intramembranous bone

Answer 12

The direct conversion of mesenchymal cells into bone

Eg. Skull neural-crest derived from mesenchymal cells divide and then coalesce into compact groups of aggregates= blastema

Question 13

Steps of intramembranous bone formation

Answer 13

1. Some Mesenchymal cells in the blastema develop into osteoblasts
2. Osteoblasts secrete osteoids (an extracellular matrix of collagen and proteoglycan that can bind calcium  become calcified.
3. When osteoblasts are surrounded by calcified osteoid they are called osteocytes
4. Many osteocytes= woven bone
5. Outer mesenchymal cells begin to form the periosteum (a membrane of cells surrounding bone)
6. The developing bone (woven bone) becomes vascularized, collagen fibres disorganized, with periosteum surrounding both sides
7. The woven bone gets reorganized on outer edges = lamellar bone

Question 14

Endochondral bone

Answer 14

Mesenchymal cells first differentiating into cartilage then later replaced by bone

Eg. Vertebral column, ribs, pelvis, limbs

Question 15

Endochondral bone formation (long bone example)

Answer 15

1. Cartilage model or framework of bone is formed and then a hollow bone cylinder called the bone collar (periosteum) develops in local perichondrium (via local intermembranous bone formation)
2. In middle of cartilage framework (diaphysis) chondrocytes hypertrophy, and begin to produce matrix, then degenerate and matrix begins to calcify
3. A Periosteal/osteogenic bud containing capillaries, osteoprogenitor cells (form osteoblasts) and mesenchymal cells invades the hypertrophied cartilage. The bud grows and lays down compact bone in shaft, creating a primary ossification centre
4. A secondary ossification centre develops at each end of the cartilage framework called the epiphysis
5. In epiphyses, cartilage continues in 2 regions: the articular cartilage and epiphyseal cartilage

Question 16

Development of axial skeleton/vertebral column

Answer 16

1. Notochord induces surround mesenchyme to secrete epimorphin
2. Epimorphin (chemoattractant) attracts scleratomal cells to area around notochord and neural tube
3. Scleratome cells form cartilage and eventually vertebrate by splitting into populations (loosely packed= cranial part, densely packed= caudal part)
4. Re-segmentation of caudal and cranial scleratome. Includes joining caudal half of one scleratome with the cranial half of the next scleratome.

Question 17

What does the re-segmentation of caudal and cranial scleratome allow?

Answer 17

Allows for he motor neurons to grow out laterally and innervate newly forming muscles from myotome

Question 18

Vertebral ossification and ribs

Answer 18

Endochondral ossification bone formation occurs from centers of the vertebral body and arches. Programmed by hox genes.

Ribs arise from segmented scleratome-derived mesenchymal condensations beside thoracic vertebrate

Question 19

Stages of early limb development

Answer 19

1. Development starts when mesenchyme cells migrate form the limb fields in the lateral plate mesoderm (limb skeletal precursors) and somites (limb muscle precursors)
2. Apical ectodermal ridge (AER) signals for the limb bud to extend. Gradients of retinoic acid and FGFs (fibroblast growth factors) occur which stimulate Hox genes and limb patterning

Question 20

Limb skeletal precursors

Answer 20

mesenchyme cells in the lateral plate mesoderm

Question 21

Limb muscle precursors

Answer 21

Mesenchyme cells in the somites

Question 22

Hox genes

Answer 22

Hox 9 & 10: Stylopod- humerus/femur

Hox 11: Zeugopod- radius/ulna, tibia/fibula

Hox 13: Autopod- carpals/fingers, tarsals/toes

Question 23

Skeletal muscle development

Answer 23

Muscle development from dermatome and myotomes

1. Dermatome – forms dermis of skin
2. Myotomes – will produce precursor myoblast cells that will give rise to Epaxial muscles (eg. Intercostal, deep muscles of back) and Hypaxial muscles (eg. Body wall, limbs and tongue)

Question 24

Long Bone Epiphyseal Cartilage (Prepubertal period) canals

Answer 24

Form from the perichondrium around the region. These canals contain venules, arterioles, nerve fibres

Osteogenic cells will be supplied to the area via the cartilage canals from the Perichondrium

Question 25

Zones of the epiphyseal cartilage

Answer 25

1. Resting Zone – non proliferative chondrocytes
2. Proliferative zone – stacked columns of chondrocytes that divide
3. Hypertrophic zone – containing large chondrocytes
4. Resorption zone – dying chondrocytes and resorption/calcification of cartilage matrix
5. Ossification zone – new bone tissue formed by osteoblasts. Osteoblasts produce osteoid over remnants of calcified cartilaginous matrix which will become ossified

Question 26

Osteon

Answer 26

the entire complex of lamellae and canal (with blood vessels and nerve)

Question 27

Haversian and Volkmann’s canal

Answer 27

Haversian: central canals in each osteon

Volkmanns: connects haversian canals

Question 28

Lacunae

Answer 28

• lay in between the lamellae
• connected to Haversian canal
• contain osteocytes

Question 29

Bone Remodeling- Cortical Compact Bone

Answer 29

Remodeling unit starts at a leading edge or cutting zone where osteoclasts break down existing bone

Then a reversal zone with a switch from resorption to formation of new bone begins and involves the osteoblasts

Closing zone where osteoblasts build new lamellae

Question 30

Bone Remodeling- Spongy Bone

Answer 30

Osteoclasts work on endosteal surface to break down matrix

Osteoblasts from endosteal surface then add more bone on same or opposite regions

Question 31

Fracture Repair

Answer 31

1. Fracture leads to blood clot. Osteocytes die on each side of fracture
2. Callus needs to form: Periosteal and endosteal cells proliferate resulting in an internal callus between opposing sides of fracture. External callus around outer broken surface if ends more (otherwise only need internal callus)
3. Osteogenic cells near blood supply form bone directly. If away from blood supply, osteogenic cells form cartilage first then remodel to bone.
   - Osteogenic cells/capillaries from living bone can invade any dead bone with help of osteoclasts
4. New osteons laid down. Original structure restored.