MSK-bone biology Flashcards
what is bone?
connective tissue consisting of a soft porous network (trabeculae) surrounded by a harder dense exterior (cortex)
what are the functions of bone (4)?
- Supports soft tissue and provides attachment site for skeletal muscles to aid movement
- Protects internal organs
- Site of Haematopoiesis
- Regulates Mineral Homeostasis – store of Ca2+
what is the diaphysis of the bone?
the long, cylindrical, main portion of the bone.
what is the epiphyses of the bone?
the proximal and distal end of bone
what are the metaphyses of the bone?
regions between the diaphysis and the epiphyses
what is the medullary cavity of the bone made up of ?
- hollow, cylindrical space within diaphysis containing:
- —>red marrow
- —>yellow marrow (adipose tissue)
what does compact bone form?
the hard exterior of bone, consisting of dense tissue with few spaces
what are osteons?
- the repeating structural units of compact bone
- each consists of concentric rings of hard, calcified extracellular matrix-lamellae
what does the lamellae surround?
-a small network of blood vessels and nerves located in a central canal (Haversian)
how are osteons in compact bone aligned to resist fracturing?
in the same direction, parallel to the length of the diaphysis, providing resistance to bending/fracturing
what are the volksmann’s canals?
exist perpendicular to the Haversian canal and connect the periosteum to the interior of the bone
what is trabecular bone?
Spongy interior of bone, consisting of a network of lamellae arranged in fine, irregular columns - Trabeculae.
how are trabeculae separated and how does this help with its function?
- separated by spaces, filled with bone marrow and are orientated along lines of stress
- allowing t bone to be lightweight-move more readily when pulled by skeletal muscle
- stress resistant to protect bone marrow
what is the periosteum?
the tough connective tissue sheath (and its associated blood supply) that surrounds the bone surface (wherever it is not covered by articular cartilage)
what is the periosteum composed of?
- an outer fibrous layer of dense irregular connective tissue
- an inner osteogenic layer that consists of cells
- has a rich blood supply and high volume of vasomotor and sensory nerves in order to respond with high sensitivity to injury
what is the endosteum composed of?
- layer of connective tissue that lines the inner surface of bone
- consists of osteoprogenitor cells and loose connective tissue perforated by blood vessels
name the 4 different bone cells.
- osteoprogenitor cell
- osteoblast
- osteocytes
- osteoclasts
what are osteoprogenitor cells?
pre-cursors of osteoblasts derived from mesenchymal bone cells
where are osteoprogenitor cells found?
- along the inner portion of the periosteum
- in the endosteum
- in canals
what are the roles of osteoblasts?
- bone forming cells of mesenchymal origin
- expressing ALP (alkaline phosphatase)
- synthesise and secreted unmineralised bone matrix in response to cytokines/ growth factors
what are osteocytes?
matured osteoblasts embedded in mineralised bone matrix
what is are the roles of osteocytes?
- maintain bone tissue in response to mechanical loading
- produce factors that regulate bone cells
which factors regulate bone cells?
- prostaglandins
- RANKL
- sclerostin
what type of cells are osteoclasts?
-motile, multinucleate cells
what is the role of osteoclasts?
bone resorbing cell
how does the structure of osteoclasts help with bone resorption?
-osteoclasts plasma membrane is deeply folded into a ruffled border (layer facing bone surface)-produce lysosomal enzymes and acids to catabolise protein and mineral components of ECM
what is bone remodelling useful for?
- used to maintain and grow the skeleton (renewal every 7-10 years)
- respond to altered mechanical requirements (Wolff’s law)
- repair damage (micro/macro features)
- response to calcium deficit
what is ALP?
alkaline phosphatase
what are the local factors involved the bone metabolism?
- prostaglandins
- cytokines
how do prostaglandins regulate bone metabolism?
-fatty acid metabolites (produced by osteoblasts) increase and decrease osteoclast activity to mediate the actions of growth factors and responses to mechanical loading
how do cytokines regulate bone metabolism?
- produced by immune cells and bone cells increase osteoclast recruitment and activity, increasing bone loss.
- sex steroids can inhibit interleukin activity
what does the bone matrix consist of?
-Inorganic Hydroxyapatite Mineral = Calcium Phosphate Salt crystals surrounding collagen fibres to provide rigidity and strength
-Organic Osteoid = 90% type I collagen - (Structural protein providing strength, flexibility)
& 10% Mixture - Growth factors- Osteocalcin (bone formation marker)/ Osteonectin Osteopontin/ Glycoproteins
what is mineralisation of osteoid promoted by?
hormonally active vitamin D3
what 2 bone types does mineralisation of osteoid by vitamin D3 produce?
- woven bone
- lamellar bone
what is woven bone?
an immature form of bone
describe how woven bone is produced.
produced when osteoblasts secrete osteoid rapidly eg in foetal bone development/ fracture repair in adults
what does rapidly formed woven bone eventually from?
remodelled to form lamellar bone in adults-stronger and more resilient
what is lamellar bone comprised of ?
regular parallel band of collagen arranged in sheets
describe how bone resorption occurs.
- Osteoclasts attaches to the bone surface at the endosteum/periosteum and form a leak proof seal at the edges of its ruffled border
- RANKL stimulates osteoclast formation and activity
- osteoclast now release protein-digesting lysosomal enzymes and acids into the sealed pocket
- the enzymes digest collagen fibres while acids dissolve the bone minerals
- degraded bone proteins and extracellular matrix minerals (Ca2+ and PO4-) enter an osteoclast by endocytosis, cross the cell vesicles and are exocytosed on the opposite membrane of ruffled border into interstitial fluid
- then diffused into nearby blood capillaries
how are bones reformed?
- small area of bone has been resorbed
- osteoclasts depart
- osteoblasts move in expressing ALP and secreting unmineralised bone matrix
what is the main role of vitamin D?
to maintain Ca2+ and PO4- at optimum serum/ blood levels by helping them be absorbed in the gut
what are adequate levels of Ca2+ and PO4- required for?
- promoting mineralisation of the osteoid ECM of bone
- functioning of skeletal muscle
how is active vitamin D made?
1- 7-dehydrocholesterol (vit D3) is found in the skin or taken in from the diet
2-it absorbs UVB to form pre-vit D
3-heat causes pre-vit D to form vit D-transported to liver
4-in the liver 25(OH)ase converts Vit D to 25(OH)D
5-in the kidney 1-alpha-(oh)ase converts 25(OH) 1,25 (OH)2D—>this is active form of vit D
what are the direct effects of activated vitamin D?
-increase Ca2+ absorption in the gut (by inducing Ca2+ binding protein expression)
-decrease synthesis of PTH (as PTH also increases Ca2+ so not needed)
-inhibits action of 1-alpha(OH)ase in the kidney (with neg feedback loop)
-increases bone resorption (by increasing RANK-L expression-increases osteoclast activity)
(OVERALL EFFECT:all increase levels of serum & blood Ca2+/PO4-)
what are the indirect effects of activated vitamin D?
increases bone mineralisation using Ca2+ and PO4-
-increase serum ca/po by stimulating osteoclast activity-so osteoblasts can reform bone with high conc of minerals required fro bone deposition
(OVERALL EFFECT: remodelling bone)
what are the causes of vitamin D deficiency?
- reduced skin synthesis
- increased melanin (which absorbs UVB)
- decreased bioavailability (due to malabsorption of fat in gut)
- decreased synthesis of 25(OH)D-liver failure
- decreased synthesis of 1,25(OH)2D-kidney disease
what are the clinical consequences of vitamin deficiency?
- muscle weakness
- osteoporosis
- rickets (children)-bone softening
- osteomalacia (adults)-bone softening
how does vit D deficiency lead to osteoporosis?
weakness of bone due to lack of balance between bone reabsorption and deposition
the inner lining of bone shaft is called? A-osteon B-periosteum C-endosteum D-osteoblast
C
long bones enlarge at the ends into: A-osteons B-periosteum C-endosteum D-epiphysis
D
compact bone is made up of: A-osteons B-trabeculae spicules C-spongy bone D-all of above
A
Bones serve all of the following functions except: A-support/ protection/ movement B-transportation of substances C-storage D-blood cell formation
B
where are osteoclasts concentrated?
endosteum
where are osteoclasts derived from?
fusion of monocytes
how are the collagen fibres arranged in woven bone?
randomly arranged collagen fibres in the osteoid
how are lamellae arranged in trabecular bone?
in a network arranged in fine irregular columns—>Trabeculae
