Biology of Skeletal Tissue Flashcards
Cartilage
Derived from mesenchymal progenitors
Avascular
Resists tension and compression
Template to bone formation
Types of Cartilage Growth
Appositional and Interstitial
Appositional Growth
Perichondrial progenitor cells differentiate into chondroblasts
Interstitial Growth
Chondrocytes divide in lacuna and synthesize matrix, giving rise to iosgenous groups
Hyaline Cartilage
Articular surfaces of the joints, fetal tissue, respiratory system
Cushions
Chondrocytes are found in lacunae
Covered by perichondrium
Elastic Cartilage
Found in External ear and auditory canal
Flexible
Elastic fibers
Fibrocartilage
Attachement of tendons and intervertebral discs
Resists deformation
Chondrocytes in rows made up of type I collagen fibers
NO Perichondrium
Chondrocyte Differentiation
Derived from mesenchymal cells
BMP –> Sox9 –> Sox5,6 –> Col2A1/ Aggrecan/ Link Protein
Sox9 tells mesenchymal cells to become chondroblasts
Sox 5,6 tells chondroblasts to become chondrocytes
Periosteum
Fibrous Layer
Osteogenic Layer
Endosteum
Bone lining cells
Contains osteoclasts
Compact Bone
Cortical Bone
Perimeter of the bone
Trabecular
Cancellous/ Spongy bone
Honeycomb like structure
Osteoblasts
Produce Osteoid and subsequent mineralization
Support osteoclast development
2 months
Bone Mineralization
Hydroxyapatite important bone mineral
Regulation of Bone Mineralization
PPi inhibits bone mineralization
Extracellular PPi levels increased by NPP1 and ANK
NPPI transforms ATP to PPi
ANK is channel for PPi
PPi cleaved by TNAP (inhibits mineralization)
Osteoblast Differentiation
Mesenchymal Cells > Pre OB > Immature OB > OB
Osteoblasts (OB) can become osteocytes or bone lining cells
Mesenchymal cells diff into pre OB by BMP –> Runx2
RunX2
Transcription factor expressed in osteoblasts
Master regulator of osteoblast differentiation
SOST (Sclerostin)
Produced by osteocytes and inhibits Wnt signaling
Inhibiting Wnt signaling inhibits osteoblast differentiation via BMP inhibition
Effects on Inhibiting SOST
Increased bone formation
Osteoblasts have lost inhibition and are creating bone like no tomorrow
Osteocytes
Imbedded in matrix lacunae Long dendritic processes in canaliculi Mechanosenor cells Regulate: osteoblast differentiation via SOST Bone Remodeling and phosphate metabolism
Osteoclasts
Form Howship’s Lacunae where they deposit acid
Attached to bone matrix via talin and vinculin (focal adhesions)
Produce carbonic anhydrase
Pump H+ into Howships lacunae via ATPase
Lifespan 2 weeks
Osteoclast Differentiation
Immature Osteoblasts produce M-CSF
M-CSF stimulates CFU-GM cell
Pre-Osteoclast forms from CFU-GM
Pre-Osteocalst Receptor RANK binds to RANKL and differentiates into osteoclast
Types of Bone Formation
Intramembraneous
Bone forms directly from mesenchyme
i.e. skull, mandible, clavicle
Endochondral
Bone replaces a cartilage template
Base of the skull, vertebrae, limbs
PTHrp
Parathyroid Hormone Related Protein
Most concentrated at the diaphysis
Signals chondrocytes to proliferate
Prevents chondrocyte hypertrophy
3 Key aspects of Bone Remodeling
Mineral Homeostasis
Repair Microdamage
Adapt to mechanical forces
Bone Remodeling Process
Takes 6-9 months
Activation > Resorption > Reversal > Formation
BMU
Basic Multicellular Unit
Contains osteoclasts and osteoblasts
BMUs tunnel longitudinally through corical bone forming new Haversian systems
Mechanical Loading vs Unloading
Mechanical loading prevents osteocyte apoptosis
Mechanical Unloading promotes apoptosis
Mechanical Loading prevents SOST signaling and promotes Wnt signaling
