factors in initiation of ossification Flashcards
The immediate conversion of mesenchymal cells to osteoblasts; occurs where? and what is the exception?
primarily in the bones of the skull, including cranial suture lines; An exception includes the periosteum surrounding the outer surface of long bones; also considered as intramembranous
what are the processes intramembranous ossification?
stage 1- Ossification Centre Formation
stage 2- Calcification
stage 3- Trabeculae Formation
stage 4- Periosteum Development
what happens in stage 1?
Mesenchyme condenses into membranous sheet
Osteoprogenitor cells found here differentiate into osteoblasts and collagen fibres surround the cells
what happens in stage 2?
Osteoblasts secrete osteoid and some are enveloped in intracellular matrix, forming lacunae and converting into osteocytes
Osteoid calcifies to form spicules of bone
what happens in stage 3?
The remainder of cells synthesize and secrete osteoid, then calcify to become woven bone trabeculae
Cancellous bone formed from interconnecting network of trabeculae, including spaces for separation (form red bone marrow)
what happens in stage 4?
The periosteum, which contains osteoblasts, constructs a bone layer beneath its surface and forms an outer compact bone layer
what is Endochondral Ossification?
This process involves the conversion of mesenchymal cells to chondroblasts, producing the cartilaginous template, and then the mineralised mode is replaced by bone.
main mode of ossification within the centra of vertebrae
1st process in Endochondral Ossification?
Condensation and differentiation of mesenchyme into chondrocytes, leads to production of main hyaline cartilage mode
2nd process in Endochondral Ossification?
Hypertrophy and division of chondrocytes occurs, hyaline model begins to calcify. As calcification progresses, diffusion of nutrients through calcified matrix dramatically reduces
3rd process in Endochondral Ossification?
Chondrocytes apoptose and hollow cartilage matrix now serves as framework for deposition of bone
4th process in Endochondral Ossification?
Due to osteogenic potential of inner perichondral cells, a thin collar of bone surrounds midpoint of diaphysis, referred to as periosteum. Above and below bony collar, periosteum continuous with perichondrium
5th process in Endochondral Ossification?
Mesenchyme near periosteum differentiate into osteoprogenitor cells and blood vessels invade calcified hyaline model
6th process in Endochondral Ossification?
Osteoprogenitor cells differentiate into osteoblasts, secreting osteoid which is quickly mineralised to bone. Osteoblasts surrounded in lacunae referred to as osteocytes (cell to cell connection through canaliculi)
7th process in Endochondral Ossification?
Primary ossification centre (POC) first appears in diaphysis of long bone, secondary ossification centres (SOCs) occur at epiphyses
8th process in Endochondral Ossification?
Epiphyseal growth plate develops soon after formation of POC at boundaries of diaphysis and epiphyses, these are important for longitudinal growth and diametric expansion until growth stops
9th process in Endochondral Ossification?
Expansion of POC and SOCs eventually replaces all cartilage with bone, including EGP, at the end of puberty. Hyaline cartilage surrounding outside of epiphyses remains; articular cartilage
what are some factors initiating ossification?
- transcription factors
what do SRY-box containing gene 9 (Sox9) do?
differentiation of mesenchymal stem cells to chondrocytes, absence can cause achondroplasia
what do Run-related transcription factor 2 (Runx2): do?
expressed in pre-hypertrophic and hypertrophic chondrocytes, and osteoblasts, consequences of removal are fatal due to lack of mineralized skeleton
what is Ihh/ PTHrP?
form an importantfeedback loopwhich regulates part of endochondral ossification
what does Ihh stand for?
indian hedgehog
what does PTHrP stand for?
parathyroid hormone-related peptide
Ihh secreted by what?
prehypertrophic chondrocytes, in turn allowing PTHrP to control the differentiation of chondrocytes near the articular surface of the growth plate
If removed, what happens to PTHrP expression
decreases, pathway ensures hypertrophic differentiation doesn’t occur too early
the Ihh/ PTHrP pathway ensures what?
This pathway normally ensures that hypertrophic differentiation doesn’t occur too early, so the number of columnar chondrocytes is maintained and hence the length of the columns. Bones are able to be formed in an organised fashion, as this loop ensures there is a balance between proliferation and maturation of chondrocytes.
when Ihh is absent what occurs?
Osteoblast differentiation is also halted when Ihh is absent.
Beta-catenin-dependent pathways are called what?
canonical pathways
Signalling without Beta-catenin are called what?
non-canonical pathways
Wnt/Beta-catenin signalling allows what?
osteoblasts to differentiate, removal from mouse models inhibited this process and increased osteoclastogenesis
Absence of Wnt3 causes what?
failure of both arms and legs to develop (tetra-amelia)
Wnt3 are what?
glycoproteins
what do Wnt3 signal?
They signal either via B-catenin-dependent pathways, which are calledcanonicalpathways, or without B-catenin, which arenoncanonicalpathways.
It has been suggested thatWnt/B-catenin signallingallows what?
signallingallows osteoblasts to differentiate.
Bone morphogenetic proteins (BMPs) are part of what?
the Transforming Growth Factor-Beta protein family
When BMPs are removed what happens?
When some are removed, can result in death or prominent defects
what do BMPs bind to?
Bind to specific membrane receptors
BMP 2: allows what?
BMP 2: allows proliferation and maturation of chondrocytes, without it chondrodysplasia develops, also significant in fracture healing and mutations can cause cleft palate
BMP 11 allows what?
BMP 11: responsible for axial skeleton patterning anterior to posterior, change in expression of Hox genes
BMPs induce what
induce Runx2 expression
FGFR3 does what?
thought to control chondrocyte proliferation, present in proliferating zone of growth plate
Mutations of FGFR3 can cause?
can cause achondroplasia
FGF18: expressed in what?
perichondrium, likely most common activator of FGFR3
FGF2: expressed in what?
limb buds, likely connections to Ihh and BMP2 expression, both pathways affected when removed
FGFR1/2 important in what?
important in endochondral ossification, particularly in limb development. FGFR1 expressed in hypertrophic chondrocytes and FGFR2 in osteoblasts
what is Mechanobiology?
A field, which focuses on how cell tissue mechanics and physical forces affect cell behaviour and tissue morphogenesis