Bone Morphology Flashcards
What is found in the bone ECM?
Collagen, calcium hydroxyapatite crystals, proteoglycans and glycoproteins
What is collagen’s function in bone?
Gives tensile strength
How are collagen helices organised?
arranged at different angles in different lamellae
Calcium Hydroxyapatite crystals function
compressive strength
How are the crystals structured?
Attached to collagen fibres by Osteonectin
What are the crystals a source of?
Phosphate ions and calcium
What evidence is there to show the function of collagen and the calcium hydroxyapatite crystals?
Add acid, will demineralise the bone leaving only collagen. The resultant bone is stretchy. Add heat, will denature the collagen leaving a very brittle bone.
Proteoglycan functions
Bind to the collagen hydroxyapatite matrix to shield the crystals from the destructive effects of temperature and chemical agents.
4 main glycoproteins
Osteonectin, osteocalcin, osteopontin and Bone Morphogenic Factor
Osteonectin function and which main cells secrete it
binds calcium hydroxyapatite crystals and collagen and initiates mineralisation. Secreted by osteoblasts and fibroblasts
Osteocalcin function and which cell secretes it
In its carboxylated form, osteocalcin binds calcium ions. Secreted solely by osteoblasts
Osteopontin function
Thought to anchor osteoclasts to mineral matrix of bone
Bone Morphogenic Factor function
induce the formation of new cartilage and bone
Main bone cells
Osteoblasts, osteoclasts and osteocytes
Osteoblast function
Growing cells which synthesise and secrete organic components into the bone matrix, such as collagen, glycoproteins and proteoglycans
Where are osteoblasts located?
localised exclusively at the bone surface
How are osteoblasts anchored and bound to one another?
Attached to the bone matrix by integrins. Bound to each other by adherent and gap junctions
What happens once the Osteoblasts have completed their function?
Begin differentiation into osteocytes and migrate into the matrix where they become entrapped by lacunae. Osteocalcin then binds calcium ions locally. Differentiating osteoblasts also secrete membrane enclosed matrix vesicles containing alkaline phosphates whose role are to increase the phosphate ion concentration in the matrix. High concentration of both these ions enable the hydroxyapatite crystals to form.
Osteocyte function and location
Inactive cells that serve as mechanosensors, detecting the mechanical load and stress on the bone and thus can trigger bone remedial action. Entrapped in lacunae within osteons
What do osteocytes produce during the transition from an osteoblast?
Dendritic processes which become surrounded by calcifying matrix that eventually become canaliculi.
What occurs in the canaliculi?
Canaliculi contain a small volume of interstitial fluid whereto diffusion of metabolites between osteocytes and blood vessels takes place
How do osteocytes communicate with one another and other cells?
Via gap junctions present at the dendritic processes
Difference in osteocyte organelle composition compared to osteoblasts
less RER, smaller Golgi and more condensed nuclear chromatin
Osteoclasts function
Essential for matrix resorption during bone growth and remodelling
Osteoclast size and nuclei number
very large, multiple nuclei
Briefly how osteoclasts work
Attach via integrins to arg-gly-asp (RGD) sequences in the matrix protein osteopontin. Form ruffled edges facing sealed Howship’s Lacuna, where they secrete acid and proteases which breaks down the bone matrix.
Connective tissues of the bone
Endosteum and periosteum
Periosteum outer layer
Outer fibrous layer of dense connective tissue, containing mainly type 1 collagen, with fibroblasts and blood vessels. Bundles of periosteum collagen, perforating fibres, penetrate the bone matrix and bind to it. Blood vessels branch and penetrate the bone too.
periosteum inner layer
more cellular, includes osteoblasts, bone lining cells and mesenchymal cells, called the osteoprogenitor cells.
What are the osteoprogenitor cells?
mesenchymal stem cells
What bones does the periosteum cover?
Outer surface of all bones but joints of the long bones
Where is the endosteum found?
covers small trabecular of bony matrix that projects into the marrow cavities (medullary cavity)
Endosteum structure
contains osteoprogenitor cells, osteoblasts and bone lining cells, within a sparse, delicate matrix of collagen fibres
Two types of bone
Trabecular (cancellous) and compact (cortical)
Where is cancellous bone found?
Epiphyses, short bone cores, around the central marrow cavity of the diaphyses,
Where is cortical bone found?
Surface of epiphyses, surface of short bones, almost entirety of long bones.
Two types of cancellous bone organisation
Lamellar bone and woven bone
How is lamellar bone characterised?
Multiple layers of lamellae of calcified matrix- organised in parallel sheets of concentrically around a central canal
What is an osteon?
A complex of concentric lamellae with a central canal (Haversian canal) containing small blood vessels, nerves and endosteum.
What is found between the successive lamellae?
lacunae containing osteocytes
What is the outer boundary of the osteon called and what it contains?
cement line, with non collagen proteins, minerals and collagen
How many concentric lamellae does each osteon have?
5-20
How do the canals communicate with each other?
Through transverse perforating (Volkmann canals) canals
What is found between the osteons?
Interstitial lamellae
What is interstitial lamellae and how is it formed?
Groups of parallel lamellae which are remainders of osteons partially destroyed by osteoclasts during growth and remodelling of bone
Other lamellae and their location and function
external circumferential lamellae, immediately beneath the periosteum. Inner circumferential lamellae, around the marrow cavities. Both enclose and strengthen the middle regions of bone containing osteons.
How is woven bone characterised?
Non-lamellar with a random disposition of type 1 collagen
What bone tissue is the first to appear in embryonic development?
Woven bone tissue
Where is woven bone found?
Embryos, in recent fracture repair, however temporary in adults. Permanently found in the insertions of some tendons and sutures of the calvaria
what is osteogenesis?
bone development
Two osteogenetic processes
intramembranous ossification and endochondral ossification
What bones are formed by intramembranous ossification?
most flat bones, such as the bones of the skull and jaw, as well as the scapula and clavicle
Where does bone formation begin?
Within condensed mesenchyme ossification centers?
What are ossification centers?
areas in which osteoprogenitor cells arise, proliferate and form incomplete layers go osteoblasts around a network of developing blood vessels
What is the first stage of intramembranous ossification?
Osteoblasts secrete organic matrix components at the cell surface in contact with existing bone material, producing a collagen rich layer called osteoid.
Osteoid location
between osteoblasts and existing bone
Next stage of intramembranous ossification
Osteoid calcifies, forming small regions of woven bone with osteocytes trapped in lacunae.
What causes the fusion of ossification centres?
continued matrix secretion and calcification
Final stage
woven bone matrix replaced by compact bone that encloses a region of cancellous bone
What gives rise to the endosteum and periosteum
mesenchymal regions that do not undergo ossification
Where does endochondral ossification take place?
the epiphyses of long bones, within hyaline cartilage . However also takes place in the majority of bones
Where does the process of endochondral ossification begin?
Occurs in the bone collar, produced by osteoblasts within the perichondrium (transitioning into the periosteum) around the diaphysis cartilage.
Bone collar function
impedes diffusion of oxygen and nutrients into the cartilage, causing local chondrocytes to hypertrophy and compress the surrounding matrix, initiating calcification by releasing osteocalcin and alkaline phosphatase
What happens to the chondrocytes?
Hypertrophic chondrocytes die, leaving empty spaces in the calcified matrix
What occurs next in endochondral ossification?
Blood vessels from the old perichondrium penetrate the bone collar, bringing osteoprogenitor cells and osteoblasts into the central region, which produce woven bone.
Where does endochondral ossification occur in the beginning of embryonic development?
Primary ossification centres of the diaphysis
Where does endochondral ossification occur later?
Secondary ossification centres of the epiphysis
Which two regions of cartilage remain after endochondral ossification?
Articular cartilage and epiphyseal plate
Where is articular cartilage?
Between joints of long bones
Where is the epiphyseal plate + function?
Connects the epiphysis to the diaphysis and allows the longitudinal bone growth in children
5 Distinct regions of cellular activity at the epiphyseal growth plate
Zone of reserve, proliferative zone. zone of hypertrophy, zone of calcified cartilage, zone of ossification
Explain each of the 5 zones
Zone of reserve- composed of hyaline cartilage
Proliferative zone- cartilage cells divide, enlarge and secrete more type II collagen and proteoglycans. Become organised into columns parallel to the long axis of bone
Zone of hypertrophy- swollen, terminally differentiate chondrocytes, compress matrix into aligned spicules. Secretes type X collagen, preventing diffusion into the matrix
Zone of calcified cartilage- chondrocytes about to undergo apoptosis release matrix containing alkaline phosphatase and osteocalcin to begin matrix calcification
Zone of ossification- formation of woven bone
Where does longitudinal growth take place?
Cell proliferation of growth plate
Process of growth of the circumference
appositional growth
Process of appositional growth
- Osteoblasts release Osteoclast Differentiation factor (RANKL) and macrophage colony stimulating factor.
- the RANKL is the osteoclast receptor activator, initiating resorption
- Integrins in osteoclast membrane seal onto the bone at the Howship’s Lacunae forming a sealing zone.
- A ruffled border develops at the contact zone
- Osteoclasts start to produce and secrete hydrogen ions via a proton pump
- Carbonic anhydrase produces more hydrogen ions by producing carbonic acid
- Chloride is exchanged for the bicarbonate produced by a membrane exchanger
- Chloride channel enables chloride to pass into the lacuna and produce HCL
- Proteases secreted to break down collagen and other proteins in the bone tissue
- Calcium and signalling peptides from the degrading bone stimulate osteoblasts to secrete matrix and replace the bone
What is the function of the sealing zone?
Able to produce a specialised microenvironment between the osteoclast and matrix
How is calcium released from bones?
Parathyroid Hormone (PTH) from the parathyroid glands stimulates osteoclasts to resorb bone matrix, releasing calcium ions.
What form of action does PTH use?
Indirect- targets osteoblasts which respond by releasing RANKL, which in turn activate osteoclasts
How are elevated calcium levels lowered?
Calcitonin, produced by thyroid gland acts directly on osteoclasts, slowing matrix resorption and bone turnover.
Where is bone marrow found?
Within spongy and cancellous portions of bone
Bone marrow components
hematopoietic cells, marrow adipose tissue and supportive stromal cells.
Bone marrow function
Store fat and formation of new blood cells
accretion definition
growth by adding multiple layers
example of accretion
appositional growth
blood supply of bones
nutrient artery and vein enter at the nutrient foramen at the centre of the diaphysis
forms metaphyseal artery and vein and then epiphyseal artery and vein
