Cellular Structure of Bone

Question 1

how is the skeleton split and what structures do they consist of?

Answer 1

axial and appendicular skeleton

axial consists of skull, neck, vertebral column and thoracic cage - midline structures

appendicular consists of upper and lower limbs, pectoral and pelvic girdles

Question 2

different functions of the skeleton?

Answer 2

• physical support, posture
• protection of vital structures/organs
• mechanical basis for movement = attachment site for muscles and tendons
• storage for salts = e.g. calcium, phosphate - which can be released when needed
• haematopoiesis - bone is the location of red marrow for the production of blood cells

Question 3

explain the organic and inorganic components of bone

Answer 3

35% of bone mass is organic - consists of collagen fibres/ ossein and some ground substance

65% of bone mass is inorganic - mostly calcium hydroxyapatite which calcifies the ossein

covered by hyaline cartilage or periosteum

Question 4

what is ground substance?

Answer 4

a substance made from non-collagenous proteins

contains:
- proteoglycan macromolecules
- multi-adhesive glycoproteins
- bone-specific vitamin K dependent proteins
- growth factors and cytokines

Question 5

describe the constitution of bone collagen

Answer 5

collagen is 85-90% type 1 collagen

some collagen V and trace amounts of VIII, XI and III

Question 6

what are the two types of microscopic structured bone?

Answer 6

woven/ immature and lamellar/mature

Question 7

structure of woven bone? where is it found?

Answer 7

woven bone is immature and primary

• random assortment of interlacing collagen fibres
• found as temporary bone in foetuses or where remodelling is happening

Question 8

what is the structure of lamellar bone?

Answer 8

lamellar bone is mature and secondary

organised in concentric layers called osteons - circular layers in compact bone
fewer cells and ground substance, more mineralised = most space is taken up with inorganic structure

Question 9

describe cortical and cancellous bone as parts of macroscopic bone structure. what they do? structure? what is the medullary cavity?

Answer 9

cortical compact bone
- forms the exterior of bone
- 80% of bone mass
- dense and provides strength

cancellous spongy bone
- forms the interior
- network of bony trabeculae that run in the direction of stress
- supports cortical bone, minimalizes weight
- spaces between the trabecular are filled with red and yellow marrow

medullary cavity in long bones is lined with cortical bone and full of marrow.

Question 10

what is the advantage of cancellous bone structure?

Answer 10

has bony trabeculae providing a high SA:V ratio - more suitable for metabolic activity

Question 11

what is the periosteum?

Answer 11

outer membrane that lines bone surfaces expect for where there are articulations

(hyaline cartilage at articulations)

Question 12

structure of periosteum?

Answer 12

outer fibrous layer, inner cellular surface

outer fibrous layer - collagen fibres parallel to the bone surface except where ligaments and tendons attach

inner cellular layer - contains osteoprogenitor cells if actively growing bone, periosteal cells in grown bone

Question 13

structure of bone cavities?

Answer 13

lined with endosteum- a layer of osteoprogenitor and bone-lining cells

bone marrow cavities contain spongy bone trabeculae. spaces between trabeculae contain red and yellow marrow

Question 14

described red and yellow marrow

Answer 14

red marrow - centre for haematopoiesis in long bones and ribs

yellow marrow - contains mesenchymal stem cells which produce cartilage. helps store fats.

yellow can revert to red marrow when needed

Question 15

what are osteoprogenitors? what stimulates their differentiation and proliferation?

Answer 15

mesenchymal stem cells in the bone marrow - can differentiate into osteoblasts and -cytes

differentiation triggered by RUNX2

proliferation triggered by IGF-1, 2 and bone morphogenic factors

can also be stimulated by electromagnetic stimulation

Question 16

what is an osteoblast? what do they do? how do osteoblasts become osteocytes?

Answer 16

bone-forming cells that secrete type 1 collagen and bone matrix proteins that form the osteoid. osteoid eventually undergoes calcification and deposited as bone lamellae.

osteoblasts can become embedded in
the calcified bone they deposit - become osteocytes

Question 17

what are osteocytes?

Answer 17

derived from osteoblasts - become enclosed in their own bone matrix and mature into osteocytes

less metabolic activities though still active, don’t secrete collagen = have less organelles and more processes reaching out

maintain bone, actively detect and respond to mechanical forces = flexing bone moves interstitial fluid through canaliculi

occupy a lacuna following mineralisation with canaliculi network - communicate with other osteocytes, systemic circulation and exchange oxygen and nutrients

Question 18

what are bone lining cells?

Answer 18

derived from osteoblasts, can revert back when needed

flat cells, few organelles = cover bone surfaces as periosteal cells (exterior) and endosteal cells (interior)

maintain and nutritionally support embedded osteocytes, regulate calcium and phosphate metabolic activity

Question 19

describe osteons

Answer 19

structures consisting of a Haversion central canal surrounded by concentric lamellar rings

Haversion canals are the centre of each osteon
- have nutrients and blood vessels
- have perforating Volkmann canals that communicate with osteocytes in lacuna = exchange oxygen, nutrients and continue nerve supply throughout bone
- canaliculi network for osteocytes in lacuna also provide nutritional support

lamellar rings provide structure
- gaps between osteons filled with interstitial lamellar
- gaps between new osteons are where old osteons were before erasure

Question 20

what are osteoclasts?

Answer 20

bone-remodelling cells = digest protein matrix via enzymes/lysosomes, dissolve minerals of old/damaged bone cells via carbonic acid

large, multi-nucleated, acidophilic. ruffled border where absorption takes place

formed by the fusion of macrophage progenitor cells, not directly related to osteoblasts

Question 21

mechanism for osteoclast bone resorption?

Answer 21

secrete carbonic acid to decalcify bone, release enzymes from lysosomes to break down bone proteins

Question 22

mechanism for osteoclast activation?

Answer 22

osteoclast precursors express RANK receptor – responds to RANK ligand (RANK-L) signalling from stromal cell surfaces or activated T lymphocytes, particularly during inflammation

RANK-RANKL pathway which promotes bone remodelling is modulated by OPG produced by osteoblasts - balance between OPG and RANKL means bone remodelling and resorption are maintained

when new bone is being formed, OPG increase and inhibit osteoclast resorption activity

balance between bone remodelling and resorption to maintain a healthy skeletal system

Question 23

how does the relationship between OPG-RANKL mediate bone remodelling?

Answer 23

balance between bone resorption and formation for maintaining bone remodelling and a healthy skeletal system

osteoblasts produce OPG for promoting bone formation

osteoclasts are derived from immune cells which respond to RANK-RANKL signalling especially during inflammation = encourages bone resorption

OPG-RANKL balance = balance between osteoblast formation and osteoclast resorption for maintenance of bone remodelling

Question 24

describe osteocytes are master controllers of bone remodelling

Answer 24

osteocytes are embedded in the bone matrix in lacunae - master controllers:

1. regulate mineral homeostasis
2. act as sensors for mechanical and chemical signals in the bone micro-environment - e.g. Ca2+ levels, hormones
   - detect changes in stress on bone tissue
3. communicate with other bone cells through dendrites = modulate osteoclast activity through the RANKL signalling pathway, modulate the balance for bone remodelling
4. detect and respond to microdamage in bone tissue by initiating bone remodelling response, activating and modulating osteoblast and -clast activity

Question 25

define intramembranous ossification

Answer 25

mesenchymal tissue directly to bone

occurs in the flat bones of the skull and face, mandible and clavicle

Question 26

define endochondral ossification

Answer 26

growing cartilage is replaced by bone - forms the growing tissue

cartilage is used as a precursor for the skeletal framework, use intramembranous ossification later on

occurs with axial and weight-bearing bones

Question 27

describe intramembranous ossification

Answer 27

process of mesenchyme directly becoming bone

mesenchyme cells as embryonic precursors to connective tissue = differentiate into osteoprogenitor cells

osteoprogenitor cells aggregate and form an ossification centre

portion of osteoprogenitor cells commit to becoming osteoblasts - move to periphery and release an inorganic mixture of collagen fibres and proteins

woven/ immature bone forms with outer and inner plates, trabeculae with spaces filled with osteoblasts and endothelial cells

remodelled into lamellar. mature bone with concentric layers of collagen, osteons

blood vessels invade trabecular spaces - can deliver oxygen and nutrients to haematopoietic cells in developing marrow

Question 28

describe endochondral ossification

Answer 28

growing cartilage replaced to form growing bone, using cartilage as a framework

mesenchymal cells differentiate into chondrocytes = cartilage-forming cells

chondrocytes produce a hyaline cartilage model for future bone

a cuff of bone forms around the shaft of developing bone for structural support

chondrocytes in the mid-region undergo hypertrophy & mature = known as the zone of hypertrophy

hypertrophic chondrocytes make and release TNAP - decreases nutrient supply, causes hypertrophic chondrocytes to die and forms the zone of calcified cartilage

osteoprogenitor cells and blood vessels from the periosteum invade the zone of calcified cartilage

osteoprogenitor cells differentiate into osteoblasts - osteoblasts lay down bone matrix in the zone of calcified cartilage = primary ossification centre forms

secondary ossification centre forms at epiphysis/ heads of long bones

process of osteoblasts laying down bone matrix continues, ossification centres grow until only the growth plates are left of the original cartilage framework

new cartilage forms in the zone of proliferation – gets reabsorbed in the zone of resorption which contributes to bone growth

the growth plate is maintained until maximal longitudinal growth has happened – epiphyseal closure occurs where epiphyseal and diaphyseal marrow cavities become confluent