Cellular Structure Of Bone Flashcards
What are the 5 functions of bone?
→ Support and movement
→ Protection for internal organs
→ Bone marrow store
→ Mineral reservoir
→ Endocrine
Where is cortical compact bone found?
→ On the outside
How is cortical bone organised?
→ In sheet like structures
→ Surrounding a hollow structure called the Haversian canal
What are the repeating units of cortical bone?
→ Osteons
What are lacunae?
→ cell sized holes within the bone matrix
What is the function of Haversian canals?
→ Allow for blood vessel penetration
Where is trabecular bone found?
→ Near the head of the bone
What is the structure of trabecular bone?
→ spongy
→ interlocking struts with spaces inbetween
What is the function of trabecular bone?
→ Makes bone lighter
What is the composition of bone in %s?
→ Protein : organic osteoid matrix 25%
→ Mineral : 75%
→ Cells
What is the function of the organic protein matrix?
→ Gives flexibility and tensile strength
What is bone mineral?
→ Hydroxyapatite
→ Calcium and Phosphate
What is the function of bone mineral?
→ Gives bone rigidity and compressive strength
What are the 4 types of bone cells?
→ Osteoblasts
→ Osteoclasts
→ Osteocytes
→ Bone marrow cells
What are the two subtypes of bone marrow cells?
→ Mesenchymal cells
→ Haematopoietic cells
What do mesenchymal stem cells make?
→ Osteoblasts and osteocytes
Where are osteoblasts found?
→ Lining the inner surface of bone
Where are osteocytes found?
→ Encased within the bone matrix
→embedded in lacunae in mature bone
→Connected via processes through canalicular channels
What do haematopoietic stem cells give rise to?
→ Lymphoid lineage - lymphocytes
→ Myeloid lineage - RBC and macrophages
→ osteocytes
What are the functions of osteoblasts?
→ Bone forming cells
→ Secrete osteoid collagen matrix of bone
→Osteoid is mineralised over time to become mature bone
→Some osteoblasts are embedded in the new bone and differentiate into osteocytes
What are the functions of osteoclasts?
→ Bone reabsorbing - digest old bone
→ seal off a portion of bone beneath them from the rest of the microenviroment using the actin ring
What is the life cycle of osteoclasts controlled by?
→ Apoptosis
What is a protease that osteoclasts secrete?
→ Cathepsin K
What do osteoclasts secrete?
→ Acid and proteases that are active in acidic environments
What do osteoclasts look like?
→ They are large and multinucleate
What are osteocytes?
→ Terminally differentiated osteoblasts
→formed from the fusion of macrophages
What do osteocytes do?
→ They lay down bone matrix (organic material that becomes mineralised)
How do osteocytes extend?
→ Via multiple dendrites via minute canals in the bone matrix
What is the function of the lacunocanalicular system?
→ Maintains communication between the bone surface and blood vessels
How is bone continually renewed?
→ Old bone is continually resorbed and new bone is laid down
→ Cycle between osteoclasts digesting old bone and osteoblasts laying down new bone
→whole skeleton has been replaced after 7 years
How does bone remodelling occur?
→ The leading edge is where cells differentiate into osteoclasts
→ Behind that the new osteoblasts differentiate into new bone
→ As the osteoblasts lay down the new bone some of them will stay in it where they are encased in lacunae
What are the phases of bone remodelling?
→microfracture
→resorption
→formation
→repaired bone
What are the 3 factors that control bone remodelling?
→ Load bearing exercise
→ Paracrine- RANKL, Wnt signalling
→ Endocrine-Estrogen, Thyroid hormone, PTH
What is the role of estrogen in bone remodelling?
→inhibits osteocyte apoptosis
→ Promotes osteoclast apoptosis
→ essential for skeletal health
What process does estrogen favor?
→ Formation over resorption
What is osteoporosis?
→ Loss of bone mass above a certain threshold
In what gender is osteoporosis more common in?
→ Women
Why is osteoporosis more common in women?
→ dramatic loss of estrogen due to menopause
What is delayed skeletal growth in men linked to?
→ Aromatase deficiency
What is RANK?
→ A surface receptor on pre-osteoclasts that stimulates osteoclast differentiation
What is the RANK ligand produced by and what does it do?
→ Produced by pre-osteoblasts, osteoblasts and osteocytes
→ binds to RANK and stimulates osteoclast differentiation
In what two forms can the RANK ligand exist in?
→ Surface bounds
→ Soluble form that is secreted from osteocytes
What does the RANK receptor binding promote?
→ osteoclast differentiation
What is OPG?
→ A soluble protein produced by osteocytes
→decoy receptor for RANKL
What does OPG do?
→ Acts as an antagonist
→ binds to RANK ligand and prevents it from binding to the receptor
What ratio controls osteoclast differentiation?
→ Ratio of RANK ligand to OPG
What are the steps for activating Wnt?
→ The frizzled receptor
→ and the co-receptor called LRP5/6 have to interace
What is the effector of the Wnt pathway?
→ beta catenin
What happens after the Wnt pathway is activated?
→ beta catenin is translocated to the nucleus where it causes transcription
What is the Wnt pathway regulated by?
→ inhibited by DKK and Sclerostin
Where is sclerostin expressed and what does it do?
→ Expressed in osteocytes
→ stops osteoblast differentiation
What do OPG and NO do?
Inhibit the differentiation of osteoclasts
What does the RANK ligand promote?
→ Promotes the differentiation of osteoclasts
What do PGE2, NO and ATP promote?
→ Differentiation of osteoblasts
What do sclerostin, DDK and SFRP1 inhibit?
→ Inhibit the differentiation of osteoblasts
What is a common bone disease?
→ Osteoporosis
What is a rare bone disease?
→ Osteomalacia
What is sclerosteosis caused by?
→ Mutation of the SOST gene
→ Inactivating sclerostin protein
What is osteopetrosis caused by?
→ Inactivating the RANK ligand
→ overgrowth of bone
What 2 changes occur during osteoporosis?
→ Thinning of the cortical bone
→ Widening of the trabecular bone
What are the three classifications of bone types?
Anatomical bones
Macroscopic structure
Microscopic structure
Describe microscopic structure of bones
→Woven bone (immature) – initial bone development
→Lamellar bone (mature)
Describe cortical bones
→long bones →80% of skeleton →Appendicular- appendages →80-90% calcified →mainly structural, mechanical, and protective
Describe trabecular bones
→vertebrae & pelvis →20% of skeleton axial →15-25% calcified →mainly metabolic →large surface area
When does clavicle growth plates fuse?
20 years old
What are the two types of ossification?
Intramembranous ossification
Endochondral ossification
Summarise intramembranous ossification
→Direct differentiation of osteoblasts from connective tissue
→Flat bones
→Osteoblasts differentiate from mesenchyme precursors
Summarise endochondral ossification
→Bones form from a cartilage model
→Long bones
→Allows rapid linear growth
Describe endochondral ossification
→Mesenchymal cells differentiate into chondrocytes that produce a cartilage model
→ becomes hypoxic and dies
→Capillaries penetrate cartilage and deposit bone inside cartilage model, forming primary ossification center.
→Cartilage and chondrocytes continue to grow at ends of the bone while medullary cavity expands and remodels.
→Secondary ossification centers develop after birth.
How is the primary ossification centre separated from the secondary?
→by growth plate
How many zones are there for linear growth?
→reserve zone →proliferative zone →hypertrophic zone →calcification zone →ossification zone
What happens in the reserve zone?
→contains small chondrocytes within the matrix.
→do not participate in bone growth
→close to the secondary ossification centre
→proliferate slowly
What happens in the proliferative zone?
→form column like structure- cells end up further away from epiphysis while undergoing hypertrophic differentiation
→expand in size and express collagen 10
What happens in the hypertrophic zone?
→Chondrocytes are older and larger than those in the proliferative zone.
→more mature cells are situated closer to the diaphyseal end of the plate.
→ they apoptose leaving behind cartilage mineral matrix which calcifies
What does Wnt signalling differentiate?
stimulates differentiation of osteoblasts from their mesenchymal precursor
What is van Buchem’s?
→Enlarged mandible
→Progressive- trapped nerves, headache
