Bone structure and formation Flashcards
What kind of tissue is bone?
Specialised connective tissue
What is bone composed of?
Living cells embedded in a mineralised extracellular matrix
Bone types
Trabecular bone
Cortical bone
Woven bone
How hard is bone?
One of the hardest CTs
Mineralised
Enamel, dentine, cementum are harder
Bone is 4th hardest
Bone constituents
30% organic (majority collagen)
45% inorganic (HA)
What is HA?
What does it do?
A hydrated crystalline material of calcium and phosphate
Hydroxyapatite provides strength
Bone matrix
Scaffold of interwoven collagen fibres (>95% type I collagen, <5% type V)
Between fibres are small, uniform, plate-like crystal of carbonated HAP
Small amounts of non-collagenous proteins, some which are unique to calcified tissues (e.g. osteocalcin)
Formula of carbonated HAP
Ca10(PO4)6(OH)2
Bone functions
Supports body and protects internal organs
Allows movement
Metabolic: haemotopoiesis and calcium homeostasis
Bone function: support
Mineralised CT when fully developed (45% HAP)
Supports body & protects internal organs
-bones of legs, pelvis, vertebrae support body
-mandible supports teeth
-bones enclose & protect brain, SC, lungs, heart, pelvic viscera, bone marrow
Allows movement
-bones provide attachment for muscles so allowing leverage e.g. leg/arm movements, ventilation of lungs
Bone function: metabolic
Haematopoiesis
-bone marrow (red marrow) is major producer of blood cells including cells of immune system
Calcium homeostasis (99% body Ca, 85% PO4)
-serum Ca2+ levels maintained by interplay between intestinal absorption, renal excretion & skeletal mobilisation or uptake
Cortical bone
Cortical/ compact/ laminar
- approx 80% of skeleton
- dense
- very strong
- forms outer layer of all bones
Trabecular bone
Trabecular/ cancellous
- porous meshwork of bone
- makes up ~20% of skeleton, mainly in axial skeleton
- bone strength also determined by trabecular microstructure - can change in disease e.g. osteoporosis
Woven bone
Forms quickly during periods of repair or rapid growth and is remodelled into lamellar bone
Periosteum
Lines outer surface of cortical bone
Bone is living dynamic tissue
Constructed to ensure maximum strength for minimum weight
Changes all the time to meet stress loads and to release Ca2+ and phosphate if required
Cell types in bone
Osteoclast: large multinucleated bone resorbing cells
Osteoblast: bone forming cells
Osteocyte: originate from Ob which have become embedded in bone matrix, involved in sensing mechanical loads and Ca homeostasis
Bone lining cells: originate from Ob, line quiescent periosteal and endosteal surfaces of bone
Osteoprogenitor cells (stromal cells): precurosors of osteoblastic lineage
Bone structure: osteocytes
Osteocytes have spider like appearance
-cell processes lie in cannaliculi and link to each other and BVs for passage of nutrients
Is bone tissue static?
No, it is continuously remodelling
Bone remodelling
Remodelling occurs at ~1-2 million microscopic sites/ skeleton at a time
Bone remodelling follows ordered sequence of events
Occurs to:
-release calcium or
-alter architecture of cancellous bone to meet new stresses
Remodelling requires cells to:
Make new bone (osteoblasts)
-cuboid cells arranged in rows on bone surface because bone can only grow by appositional growth
Break down existing bone (osteoclasts)
Phases of bone remodelling
Starts with resorption phase: bone ECM destroyed and removed
-takes ~3 weeks/ site
Bone formation phase follows: new ECM formed and mineralised
-takes ~3-4 months/ site
Mechanism of bone remodelling
- Resorption initiated by recruitment of osteoclast precursors to remodelling site
- Oc precursors mature into Oc
- Bone lining cells erode a little ECM and leave remodelling site
- Oc bind to ECM exposed by bone lining cells and digest bone matrix with enzymes to form resorption pit
- Oc stop digesting matrix & die by apoptosis
- Ob precursors recruited to remodelling site
- Ob precursors develop into mature Ob
- Ob make new ECM to fill resorption pit made by osteoclasts
- When synthesis of matrix is complete, new bone surface becomes covered in bone lining cells
- osteoblasts trapped within ECM become osteocytes
Bone formation
Required to produce new bone
-during formation of skeleton
-during fracture repair
-during tooth socket healing after extraction
First type of bone laid down is woven bone
-trabeculae are disorganised and cannot bear weight until remodelling occurs
2 types of bone formation in skeleton
- Bone formed directly from condensed mesenchyme or ectomesenchyme = intramembranous ossification (IMO)
- Cartilagenous precursor of bone is formed and replaced by bone as it grows = endochondral ossification (ECO)
- ECO more common: all bones outside skull formed this way except clavicle
- IMO only occurs in neurocranium and viscerocranium of skull & clavicle
- Basicranium formed by ECO
Intramembranous ossification
Mesenchymal stem cells condense, differentiate into Obs and secrete ECM (osteoid) in long strands
Obs lay down bone mienral on strands of osteoid
COnsecutive growth rings of osteoid (lamella) added on to trabecula to > thickness
Further bone growth by cycles of osteoid secretion and mineralisation (appositional growth)
Multiple trabecula within developing bone contact one another to form lattice structure
Areas of bones may completely fill-in with mineralised osteoid (compact bone)
Bones containing lattice structures called primary cancellous bones
Most bones are mixtures with compact outer surface & cancellous interior
Intramembranous ossification (Obs and Ocs)
- Mesenchymal cells condense and differentiate into osteoblasts
- Osteoblasts lay down osteoid
- Some cells remain in bone (osteocytes) and others on the surface as osteoblasts
An osteon
Haversian system
Defects in intramembranous ossification
Cleidocranial dystosis: rare genetic disorder that interferes with IO (skeletal dysplasia)
~1/ 1 million affected
-autosomal dominant (defect in RUNX2 gene)
-neurocranium underdeveloped
-viscerocranium underdeveloped with severe dental maocclusion, delayed formation
-large head and frontal bossing
-clavicles reduced or absent: characteristic feature
Endochondral ossification
1) Miniature cartilage replica of bone is formed by differentiation of mesenchymal or ectomesenchymal cells into chondroblasts which mature into chondrocytes
2) Cartilage grows in specific direction - by interstitial and appositional growth
3) Cartilage converted into bone
Epiphysial growth plate
Proliferation zone -parallel columns of dividing cells -formation of ECM Hypertrophic zone -significant increase in cellular size (5 fold) -matrix reduced to thin struts -down regulation of ECM -production of factors to stimulate blood vessel ingrowth Cartilage/ bone interface -cartilage matrix mineralisation -chondrocyte apoptosis (cell death) -ingrowth of BVs -production of new bone on mineralised cartilage -matrix
Bone formation routes in fracture healing
Impact Induction Inflammation Soft callus Ossification Remodelling
Achondroplasia
Recessive genetic condition that affects bone formation via ECO
-autosomal dominant
-incidence 1/ 20,000
-most common form of dwarfism
All bones formed by ECO reduced in length
-trunk and limbs short (drawfism)
-basicranium short: middle 1/3 face sunken producing ‘dish-face’ profile with Class III malocclusion
Achondroplasia genetic defect
In gene for FGFR-3, a membrane receptor that is important in response of chondrocytes to growth factor during development of cartilage ‘template’
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