Bone Function, Structure and Development Flashcards
What is bone?
A mineralized collagen-rich matrix which is very rigid and strong while still retaining some degree of flexibility
What are the properties of bone that enables its function?
- Resistance to compression: inorganic content
- Resistance to tension: organic matrix
What are the functions of bone?
- Houses bone marrow
- Calcium homeostasis
- Protects vital organs
What are the different types of bone cells?
- Osteoblasts
- Osteocytes’
- Bone lining cells
- Osteoclasts
What is the bone structure?
- Bone matrix/ mineralisation
- Bone remodelling
- Bone development: intramembranous, endochondral
What are the different parts of long bone anatomy?
Top to bottom: -Epiphysis -Metaphysis -Diaphysis (symmetrical)
What is the Epiphyseal Growth Plate?
- Specialised zone of cartilage
- Lies between epiphysis and metaphysis
- Site of longitudinal growth
- ‘Closes’ at/ after puberty
- Long bone growth stops
Describe the macroscopic organisation of bone
- Cortical (70%)= compact
- Trabecular (30%)= cancellous, medullary, spongy bone
What type of bone is each part of long bone made of (macroscopic organisation)?
- Proportion of cortical/ cancellous bone varies in different parts and types of bone
- Mid bone/ diaphysis= most cortical, little cancellous bone
- End of bone/ epiphysis= predominantly cancellous bone
Describe compact/ cortical bone
- Provides most structural support
- Resists bending and torsion stresses (thicker in mid part of bone)
Describe the microscopic structure of cortical bone
Osteons/ Haversian canals -Main structural unit of cortical bone -Bone cylinders 2-3mm long -8-15 concentric lamellae 0.2mm wide -Axis parallel to long axis of bone -Central cavity with blood vessels and nerve Volkmann's canals -Carry blood vessels from periosteum to Haversian system
Describe the microscopic structure of cancellous/ trabecular/ spongy bone
- Found inside cortices
- Forms interconnecting network of plates/ trabeculae
- Provides large surface area for metabolic functions
- Marrow space between bone trabeculae
Describe cancellous/ trabecular bone
- Provides strength without disadvantage of weight
- Organisation of trabecular plates is purposeful
- Arranged along lines of maximum mechanical stress (allows transmission of loads, support areas of maximum stress)
- More metabolically active than cortical bone (larger surface area)
What are mechanical loads transmitted through?
Hip joint to the trabecular bone of the femoral head towards the femoral cortical bone
Describe the composition of bone
- Organic 35% (osteoid)= Type 1 collagen, non collagenous proteins
- Inorganic 65%= calcium hydroxyapatite
What is osteoid?
- Unmineralised bone matrix= produced by osteoblasts
- Type 1 collagen (90%)
- Non collagenous proteins= osteocalcin (marker of bone formation), osteonectin, osteopontin, growth factors
Describe the microscopic organisation of bone matrix
Lamellar bone
-Type 1 collagen fibres laid down in parallel sheets/ lamellae
-Structurally very strong
Woven bone
-Collagen fibres randomly arranged
-Mechanically weak
-Formed when bone is being produced rapidly e.g. foetus or fracture
Describe what each bone cell types do
- Osteoblasts= bone-forming cells
- Osteocytes= a mature osteoblast surrounded by bone matrix
- Osteoclasts= function in resorption and degradation of existing bone
- Osteoprogenitor cells= osteoblast precursors
How are osteoblasts created?
- Derived from osteoprogenitor cells
- Formation and proliferation of preosteoblast cells from stem cells requires signalling through the Wnt-frizzled-Lrp5-beta-catenin signalling pathway
- Osteoblast differentiation is controlled by the transcription factors Runx2 and osterix
- In the absence of either Runx2 or osterix, no osteoblasts are formed
- Mesenchymal to bipotential to preosteoblast to osteoblast
What are the functions of osteoblasts?
- Produce and deposit osteoid
- Regulate osteoclast differentiation/ function= RANKL-RANK interactions
- RANKL= Receptor Activator of Nuclear Factor K B ligand
What is the fate of the osteoblast?
Life span 6 months
- Osteoid production
- 10-15% entombed in bone- differentiate into osteocytes
- Others die by apoptosis or differentiate into lining cells on quiescent bone
What are osteocytes?
- Most common cell in bone
- Reside in lacunae in cortical and trabecular bone (connect to other osteocytes, osteoblasts and osteoclasts via long cytoplasmic processes)
What are the functions of osteocytes?
Regulation of bone remodelling Calcium homeostasis (responds to increasing PTH levels by inducing rapid calcium release= osteocytic osteolysis)
What happens in regulation of bone remodelling?
- In response to local (biomechanical) or systemic e.g. parathyroid hormone (PTH) signals
- Increases osteoclast formation by increased expression of RANKL = bone resorption
- Inhibits osteoblast formation by production of Sclerostin= decreased bone formation (Sclerostin production inhibited by PTH and mechanical loading= increased bone formation)
What are osteoclasts?
- Monocyte/ macrophage derived multinucleate giant cells
- Formation regulated by growth factors and interactions between RANK (expressed by osteoclast lineage) and RANKL expressed by stromal cells/ osteoblasts/ osteocytes
Describe RANK-RANKL interactions
M-CSF and TNF produced by stromal cells induces expression of RANK by osteoclast precursors
- induce precursor cell fusion and increase osteoclast activity
- Regulated by Osteoprotegerin (OPG) a decoy receptor that binds RANKL and inhibits osteoclast formation preventing excessive bone resorption
- OPG secreted by osteoblasts and stromal cells
What are the actions of osteoclasts?
- Bind to mineralised bone surface (integrins)
- Resorb bone by production of: acid to release calcium, proteases to breakdown organic matrix
- By-products of bone breakdown and osteoclast enzymatic activity are used as markers of bone resorption: detected in blood or urine, Type 1 collagen fragments (N- and C- terminal cross-linked telopeptides), Tartrate-resistant acid phosphatase (expressed by osteoclasts)
What are the mechanisms of bone formation and skeletal development?
- Intramembranous ossification= osteoid laid down by osteoblasts within loose fibroconnective tissue of a fibrous membrane
- Endochondral ossification= osteoid deposited on cartilage scaffolds
Describe intramembranous ossification
- Formation of skull, maxilla parts of clavicle/ mandible
- Subperiosteal bone growth
- Fracture repair
Describe the process of Intramembranous Ossification
A: Mesenchymal stem cell proliferation in fibrous tissue, Formation of cluster/ nodule
B: Differentiation into osteoblasts- formation of ossification centre, Production of osteoid (woven)
C: Mineralisation of matrix (osteoid), Osteoblasts embedded in matrix- osteocytes
D: Blood vessels become entrapped/ grow in, Bone remodelled into lamellar trabecular bone
Describe the process of Endochondral Ossification
- Osteoid deposited on preformed cartilage: development of most of the skeleton, growth plates, fracture repair
- Programmed changes in chondrocyte: hypertrophy, matrix vesicles, type X collagen secretion, chondrocyte death
What are the primary centres of ossification?
Genetically predetermined sites and times of ossification in diaphysis of cartilage bones in utero
How are the primary centres of ossifications created?
- Hyaline Cartilage ‘Model’
- Periosteum forms
- Formation of a bony collar
- Chondrocyte hypertrophy
- Matrix calcification
- Osteoprogenitor and blood vessel ingrowth
- Primary centre of ossification
How are secondary centres of ossification formed?
- Ossification in epiphysis at or after birth
- Similar process to that of primary centre formation
- Line of cartilage between primary and secondary centres= epiphyseal growth plate
How does the epiphyseal growth plate work?
-Site of continued enchochondral ossification during growth
Longitudinal growth:
-Regulated by complex networks of nutritional, cellular, paracrine, and endocrine factors (including growth hormones, IGF-1, thyroid hormone, glucocorticoids, androgens and oestrogens)
-Rapid growth occurs at puberty and when there is plentiful nutrition
Describe longitudinal bone growth
- The cartilage model grows in length by continuous proliferation of chondrocytes
- Chondrocytes differentiate and hypertrophy
- Cartilage matrix calcifies
- Blood vessels/ chondroclasts invade and remove calcified cartilage
- Osteoblasts deposit bone on residual cartilage struts
What are the zones of the epiphyseal growth plate?
- Resting Zone= normal chondrocytes
- Proliferative Zone= chondrocytes proliferate, form stacks
- Hypertrophic Zone= chondrocytes enlarge, secrete alkaline phosphatase, Type X collagen
- Calcification Zone= chondrocytes die, matrix becomes calcified
- Ossification Zone= osteoprogenitor cells and blood vessels invade calcified cartilage, new bone laid down
- Remodelling Zone= struts if cartilage with bone remodelled into trabecular bone
Describe cessation of bone growth
Growth stops when the epiphyseal growth plates close
Varies at different sites
Genetically determined (inherited height)
-Oestrogens/ Androgens initially increase GH secretion in early puberty and increase bone growth but later induce closure of growth plates
-Premature closure of a growth plate results in a shortened bone
What are the pathological causes of growth arrest?
Local hyperaemia -Infection: osteomyelitis -Juvenile chronic arthritis -Arteriovenous malformation Trauma Metabolic conditions
Describe growth plate abnormalities
Defects in chondrogenesis give rise to skeletal dysplasias and short stature
-Achondroplasia
-Achondrogenesis type 2
-Multiple epiphyseal dysplasias
Endocrine abnormalities can give rise to increased or decreased bone growth
-Giantism
-Hypopituitarism
What is Achondroplasia?
- Mutation in fibroblast growth factor receptor 3 (FGFR3)
- Receptor constitutively active
- Decreased chondrocyte proliferation and hypertrophy
What is Gigantism?
- Excess growth hormone production before puberty
- Increased longitudinal bone growth
What is Acromegaly?
- Excess GH production
- Growth plates closed
- Increased bone formation
