Connective Tissue (T-T) Flashcards
Origins of CT and cells within CT
Mesenchymal: Precursors to all of the CT family!
- Gives rise to Osteoprogenitors, Fibroblasts, Chondrocytes.
- All of these give rise to cells that make ECM components.
- Osteoprogenitors
- -> Osteoblasts –> Osteocytes
2. Fibroblasts (pre-eminant cell)
gives rise to:
--> Myofibroblasts
--> Adipocytes
--> Smooth muscles
or shifts into:
--> osteoprogenitor
--> chondrocytes
needs to be highly regulated or you're Fucked
very diverse secretory machines
Mesenchymal cells
Precursor to all of CT family
Function in embryogenesis and/or stem cells for new CT
Osteoblasts
osteoBlasts Build Bone
- actively secretes osteoid
- secretes matrix vesicles that contain elements for calcification.
- -> Enzymes inside vesicles are activated and ppt hydroxyappetite (Ca2+ and PO4). This ruptures the vesicles and activated cascade of mineralization in the matrix.
Osteocytes
derived from osteoblasts that are trapped in bone matrix in a lacuna
- also build bone
- extends canaliculi
- form gap junctions
What are some cells not made in CT but resides in the ECM?
aka “Immigrant blood derived cells”
White blood cells
- Lymphocytes
- Macrophages
- Neutrophils and Eosinophils
- Mast cells
- Osteoclasts
-migrate from blood into connective tissue
What are white blood cells produced from?
Hematopoietic cells in bone marrow
blood cell precursors
Macrophages
large engulfing cells that phagocytose cells, ECM, ect
Act as signaling centers:
- Stimulates endothelial cells to undergo angiogenesis
- remodel damaged/undamaged tissue
-Tumor growth is aided by macrophages: supply blood
Mast cells
secretory cells, when stimulated, release substances that promote swelling in CT
- imp. in allergies
Osteoclasts
derived from blood monocytes (which originate from hematopoietic stem cells in BM)
Function in bone resorption and remodeling.
Connective tissue function
Very dynamic
- Provide mechanical strength/support
- Conduct/control exchange of nutrients, metabolites, signaling ligands
- Directly control behavior and functions of cells that contact CT matrix (ECM)
- control epi polarization/shape
- guide/regulate cell migration through matrix
- control cell proliferation, diffferentiation
- tissue formation, organization, modification during disease
- inflammation and repair
ECM
- What is it?
- What is the central CT cell type that makes the components of the ECM?
extracellular fibers embedded in gel-like mix, “ground substance”
-Fibroblasts
Fibroblasts produce certain components of the ECM, name some.
fibrous proteins
proteoglycans
signaling compounds (solutes)
Two types of (extracellular) fibers
- collagens
2. elastins
3 Types of Collagens
- Fibrillar collagen
- Fibril- associated Collagen
- Network-forming collagen
Fibrillar collagen
Consists of Collagen Type I and forms long, thick, rope like collagen bundles (fibrils)
Fibril-associated Collagen
make thin fibers connecting basal lamina to fibrillar collagen
also links fibrillar collagen to eachother
Network-forming collagen
Consists of Type IV and form very thin fibers and form interlaced networks that form scaffold for basal lamina
Pop quiz!! What causes scurvy?
Non hydroxylation of proline residues of collagens
caused by vit C deficiency
Collagen is synthesized ______ and modified ______ and secreted and further modified _____
- intracellularly
- intracellularly
- extracellularly
N-telo peptides
N-terminal fragments cleaved off from collagen outside of the cell
- clinically important: levels in urine/blood diagnose imp. CT/Bone diseases
Elastins
what are they?
what are they made of?
elastic fibers that are highly resilient/distend-able
made of elastin and fibrillin secreted by fibroblasts/smooth muscles
One important role CT has is inflammation and wound repair.
What are the sequences of events that occurs?
- Inflammation and blood clotting
- new tissue formation/proliferation
- stimulates fibroblasts to release cytokines and growth factors - Tissue remodeling
What are Histamines secreted by during an immune response?
Mast cells to promote endothelial permeabilization
What are bone and cartilage?
Specialized connective tissue
2 Functions of cartilage
- provide resilient/pliable support structure
- direct formation and growth of bone
FYI: in the fetus, large amt of cartilage is replaced by bone
Chondrocyte
- function
- where they arise from
-make cartilage matrix and tissue of ECM
(which encases them in matrix and come to reside in a LACUNA)
- chondrocytes come from perichondrium
perichondrium
external layer of CT that surrounds cartilage that contains MSC/fibroblasts that gives rise to chondrocytes (which makes cartilage matrix/tissue)
Describe how cartilage grows in fetus and children vs adults
Fetus/Children: cartilage grows dramatically, and serves as template for conversion into bone. = good
Adults: only articular surfaces of bones retain cartilage tissue. Limited repair ability.
Cartilage still retains capacity to convert to bone = bad
3 basic types of cartilage
- what are they distinguished by?
- what are they?
distinguished by type of matrix they contain
- Hyaline cartilage (most prominent)
- Elastic cartilage
- Fibrocartilage
Hyaline cartilage
-what is it made of?
full of thin collagen fibrils, proteoglycans and hyaluronic acid,
Elastic cartilage
-what is it made of?
contains thin collagen fibrils, proteoglycans as well
-also contains shit ton of elastic fibers and interconnecting lamellae sheets
Fibrocartilage
-what is it made of?
contains large bundles of densely packed fibrous collagen for tendons
(tough)
Cartilage is avascular, how does it overcome this issue?
It contains no blood vessels within its matrix, so all of the nutrients and metabolites it needs must diffuse to and from the perichondrium, facilitated by large amounts of hydrated glycosaminoglycans.
Different cell types found in bone
- osteoprogenitor
- osteoblasts
- osteocytes
- osteoclasts
How is bone matrix unique/different from most CT?
It contains lg amts of hydroxyappetite (crystallized Ca2+ and PO4)
(meaning matrix is mineralized/calcified)
Components of bone ECM
- Different cell types
- hydroxyappetite/proteoglycans/glycoproteins
- Haversian canals
- Osteon
- Volkmann’s Canal
Haversian canals
channels that traverse long bone axis through compact bone
-surrounded by lammellae in concentric rings
Osteon
“haversian system”
Lamellae + haversian canal
Volkmann’s Canal
Link haversian canals to eachother
Osteoid
unmineralized ECM of bone
-secreted by osteoblasts
2 processes that lead to bone formation
- Intramembranous ossification
- in absence of pre-made cartilage tissue - Endochondral ossification
- made from cartilage tissue (cartilage model)
Describe steps of Intramembranous ossification
- Condensation: In CT, mesenchymal cells come together
- Transform into Osteoprogenitors
- Differentiate into Osteoblasts
- Islands of Osteoblasts secrete osteoid
- More islands convert/join
- Trabecular network of bone forms- BV grow in network
- Bone matrix calcifies
Describe steps of
Endochondral ossification
- Mesenchymal cells –> Chondrocytes
- Chondrocytes secrete matrix and encase self in lacuna
- Cartilage continues to grow via appositional and interstitial growth
- Diaphysis receives signal telling mesenchymal cells –> osteoprogenitors instead
- Perichondrium transforms to periosteum
- Chondrocytes enlarge/cartilage matrix calcify = signalling osteoclasts to degrade
- Overall, osteoblasts and osteoclasts work together to calcify cartilage and deconstruct chondrocytes
(continued endochondral growth promotes lengthwise growth of bone)
Appositional growth
growth of cartilage at surface (width/diameter - ONLY BY APPOSITIONAL GROWTH)
- In perichondrium at cartilage surface, mesenchymal/fibroblasts –> chondrocytes = more hyaline matrix
Interstitial growth
growth of cartilage from within
- Chondrocytes embedded in matrix continues to proliferate within their lacuna and secrete ECM = internal growth
(because bone cant grow, but cartilage can lengthwise, then bone replaces the cartilage)
Epiphyseal plate
growth plate
where secondary ossification centers are and where “growth” of long bones occur until full length of bone is achieved
-replaced by epiphyseal line in adults
Diaphysis
Midshaft of long bone
where primary ossification centers are and where “growth” of long bones occur (bone eating up the cartilage)
Sequence of events that occur in bone remodeling
Once bone is already formed: lots of turn over
- periosteum forms on surface of cartilage (from perichondrium)
- osteoclasts become activated in specific regions and begin bone resorption
- osteoclasts lay down new blood vessels and nerve pathways
- osteoclasts signal osteoblast migration/secretion
- osteoblasts initiate mineralization of osteoid (bone matrix)
Where does most of bone resorptive activity occur?
endosteal surface
defects in bone remodeling
-give examples of diseases
- osteoporosis: defective bone formation = decrease in bone mass
- osteopetrosis: defective bone resorption = increase bone mass
- osteomalacia rickets: abnormal increase in uncalcified osteoid = bow legged
- FOP: bony formation in loose CT where lymphocytes reside
What is bone and cartilage regulation mediated by?
- short-ranged signals
- long-ranged signals
- mechanical stress
- neuronal stimulation
short-ranged signals
produced in local bone environment
contains Bone Morphogenic Proteins (BMPs),
- can stimulate chondrogenesis or osteogenesis
- control bone development and remodeling turn over
Long range signaling examples
Calcitonin
PTH
Vit D
Calcitonin: increase Ca2+ deposition/uptake, and decrease osteoclast activity
Parathyroid hormone: increase Ca2+ resorption in blood, and increase osteoclast activity
Vit D: stimulate Ca2+ uptake from intestine
