skeletal system Flashcards
listen to lec slide 13 onwards
4 main functions of skeletal system
mechanical - support attachment muscles, ligaments, tendons
protective - internal organs
haematopoiesis - blood cell formation
metabolic - reserves of calcium and phosphate
2 types of bone
trabecular bone (inner)
cortical/ compact bone
what are bones made up of (3)
water
protein (collagen type 1 fibres, growth factors, matrix proteins)
minerals (mineralised with hydroxyapatite)
chemical formula of hydroxyapatite
Ca10(PO4)6(OH)2
what % of bones does water make up
20%
what % of bones do proteins make up
35%
what % of bones do minerals make up
45%
what is the role of hydroxyapatite
makes bones rigid, allows collagen to be stronger in bones than skin
3 cells bones are connected with
osteoclasts
ostoblasts
osteocytes
how are osteoclasts formed
mononucleated precursor cells
fuse together
multi-nucleated osteoclast progenitor cell
mature
active osteoclasts
function of osteoclasts
break down/ remove bone
function of osteoblasts
synthesise new bone by laying down collagen fibres
fibres then mineralised by hydroxyapatite - stronger
where are osteoblasts located
bone surface
where are osteoclasts located
bone surface
where are osteocyte cell bodies located
in bone cavity called lacuna
where are osteocyte projections located
tunnels in bone called canaliculi
function of osteocyte projections
communication throughout bone
where do osteocytes originate from
osteoblasts trapped in the bone
evidence suggests ___ release collagen fibres so may have a role in building bone
osteocytes
bones have ____/____ due to load/ mechanical stress so require constant repair
micro-breaks/ micro-fractures
microfractures damage osteocyte projections, osteocytes release signals to osteoclasts and osteoblasts to begin bone remodelling
what is the bone remodelling cycle (4 steps)
quiescence - aka bone lining cells (inactive)
when active, reabsorption (cells recruit osteoclast to remove damaged portion of bone)
reversal (osteoblasts recruited, lay down new collagen fibres to replace bone)
formation (osteoblasts) - mineralisation
returns to quiescence again
___ must be equal to ___ for healthy bones
bone loss/ reabsorption
bone gain/ synthesis
what is bone reabsorption
removal of bone tissue
how does bone reabsorption occur (osteoclast function)
osteoclast breaks down hydroxyapatate/ tissue in bones, release minerals
calcium transferred from bone to blood
can be used elsewhere in the body
post menopause there is a dec. in oestrogen production which impacts osteoclasts. how and why
oestrogen inhibits maturation of osteoclast progenitor cells into mature ostoclasts that reabsorb bone
RECHECKhow is bone remodelling induced
microfractures damage osteocyte projections, osteocytes release signals to osteoclasts and osteoblasts to begin bone remodelling
extensive bone remodelling can cause
hypercalciumia
in bone reabsorption, calcium transferred from bone to blood, can be used elsewhere in the body. example of use
pregnancy, female bone density dec
as activated osteoclasts to break down skeletal structure and release calcium for developing embryo
post menopause dec. oestrogen production
oestrogen blocks ostoclasts
dec blocking, inc bone breakdown potentially leading to osteoporosis. treatment?
HRT - admin exog oestrogen
what is an osteoclast progenitor cell
multiple mononucleated cells formed into a multinucleated progenitor cell (not yet mature- no ruffle border)
eventually matures over time for bone reabsorption
hetereotopic assification (HO)
bone formation in wrong place
what causes hetereotopic assification disease
single point missence mutation of activin A receptor type 1 (ACVR1)
(AA R for H at 206 in GS domain)
activin A receptor type 1 (ACVR1)
mediator of bone morphogenic proteins
osteosclerosis
abnormal hardening of bone, inc bone density - overactivation of osteoblasts
how common is pagets disease
1-3% in older than 45-55
10% in older than 80
osteoporosis
reduction in bone density due to inc bone reabsorption - more fragile
inc osteoclast activity
more common in women
final correct - oestrogen __ osteoclast maturation. women are thus more at risk of osteoporosis
promotes
mutation of ___ results in fibrodysplasia ossificans progressive
ACVR1
Studies have demonstrated that the thalidomide metabolite _______ can impair angiogenesis
CPS49
3D co culture models
learning about these cells has become easier through 3d co culture models, using primary human osteocytes/blasts/clasts, which express typical markers like RANKL, ALPL after being cultured
current research focus to learn abt these cells
in vitro bone models are difficult to create, so focused on recreating certain bone aspects like tumour models or bone marrow
fibrodysplasia ossificans progressiva
rare
progressive heterotropic ossification of soft tissues forming skeletal tissue instead following trauma (e.g. dental work)
cause - ACVR1 gene substitution mutation dysregulating BMP bone morphogenic protein signalling
fibrodysplasia ossificans progressiva treatment efforts/ detetcion
diffiicult to detect, uncurable
patients can have slightly different secondary symptoms - e.g. some mental impairment, some alopecia - inc difficulty in management and early diagnosis
oct 2023 case study
5 year old girl - knees grown inwards, stunted growth, teeth issues
diagnosed with hyphophosphatemic rickets and growth hormone deficiency
treatment failed, genetic testing taken place
discovered mutation linked to amelogenesis imperfecta (AI) which tends to just affect tooth enamel , but mutation caused systemic phosphate loss
COMPLEX PATHOPHYSIOLOGY OF BONE DISORDERS
why is paget’s disease difficult to diagnose early
can be asymptomatic, can have varying symptoms like deafness and bone pain
paget’s disease possible causes - 3 but unconfirmed what it acc is ygm
mutation in gene that produces sequestome 1 which is involved in osteoclast function, leads to inc susceptibility of paget’s disease
genetic/ environmental factors
initiated by slow virus as nuclear inclusion of viral component in osteoclasts found in pd patients
paget’s disease progression
excessive osteoclast bone resorption, followed by compensatory osteoblast activity forming unstable bone and abnormal bone remodelling
clinical gaf
hypercalciumia
osteosclerosis
osteoporosis
fibrodysplasia ossificans progressive
paget’s disease
future advancements
research - 3D co culture models
