Connective tissue Flashcards
What are the functions of connective tissue?
- provide multiple attachments linking tissues and organs together
- defend against infectious agents
- control nutrient/metabolite exchange with blood and signaling ligands that communicate with different organ cell types
- directly control the behavior and functions of cells that contact the connective tissue matrix (control inflammation and repair due to injury, cell proliferation, guidance and regulation of cell migration through the matrix)
What are mesenchymal stem cells (MSCs)?
- precursors to all connective tissue family members
- prominent in embryogenesis
- small number persist through adulthood to function as stem cells for new connective tissue
What are myofibroblasts?
- derivatives of fibroblasts
- capable of smooth muscle like function
- found in connective tissue that require a contractile function
- often found in wound sites and contribute to retraction of scar tissue
What do lymphocytes become in the connective tissue?
lymphocytes (B cells, T cells, plasma cells)
What do basophils become in the connective tissue?
mast cells
What are the functions of lymphocytes?
immunity/defense against diverse foreign agents
What are the functions of neutrophils?
fight bacterial and parasite infections
What are the functions of eosinophils?
fight bacterial and parasite infections
What are the functions of mast cells?
inflammation control
What do monocytes become in the connective tissue?
macrophages
What are the functions of macrophages?
- microbe defense;
- tissue morphogenesis, angiogenesis (blood vessel development), and repair
- removal of damaged tissue
- remodeling of normal tissue
What are the functions of osteoclasts?
- phagocytic cells that are derived from blood monocytes
- function in bone resorption and remodeling
What is the ground substance?
gelatinous fluid that fibrous proteins are embedded in the connective tissue
What is the structure of each collagen molecular unit?
trimer of three intertwined polypeptide chains that forma fairly rigid rope like triple helix
What is fibrillar collagen?
- form fibrils (large bundles)
What are fibril-associated collagen?
- very thin fibers
- assemble into interlaced tissue networks that form porous sheets (can connect fibrils)
What are network forming collagen?
- thin fibers that form sheets, interlaced networks that form porous sheets
- part of the basal lamina
What is the central CT cell type that makes the components of the ECM of most connective tissues?
fibroblasts
Where are collagens translated?
ER
How are collagens transferred out of the cell?
- after being modified in the Golgi, in a vesicle
- assembled into a triple helix
How are collagens modified extracellularly?
- N- and C- termini of collagen are cleaved by specific proteases
- N- termini fragments are called N-telo peptides
Why are N-telo peptides clinically important?
- N-terminal fragments
- their levels in urine and blood are used to diagnose important connective tissue and bone diseases
What proteins do elastic fibers contain?
elastin and fibrillin
How do elastic fibers function?
- stretchable and resilient fibers and sheets
- predominantly random coil conformation that can be stretched upon exertion of force
What does the ground substance contain?
- proteoglycans
- variety of other secreted proteins and glycoproteins (e.g. proteases)
- many other small and large organic compounds
- water and inorganic solutes
- membrane vesicles (pinched off from cells)
What are proteoglycans made of?
- glycosaminoglycans (GAGs) and protein core
What is hyaluronic acid?
GAGs not attached to a protein core
What are three important properties of GAGs?
- highly negative charged (very hydrophilic)
- rigid extended structure causes them to readily form gels (promote hydration of the ground substance to allow diffusion of small metabolites but tend to inhibit movement of large structures)
- some proteoglycans can also bind to and inactivate or activate other proteins
What do the signaling compounds do that are released by mast cells, fibroblasts, and other white blood cell derivatives in response to a wound?
- increase water permeability of capillary endothelia leading to swelling
- increase cellular permeability of endothelia to promote migration of monocytes, lymphocytes, and other blood cell into the CT
- attract migration of white cells to the site of the wound (chemotaxis)
- stimulate proliferation of fibroblasts and differentiation of monocytes into macrophages
What does secreted histamine do in response to a wound?
- secreted by mast cells
- promote endothelial permeabilization (water flux and swelling)
What do secreted cytokines do in response to a wound?
- signal long distance to hematopoietic tissue to stimulate productions of more white blood cells
How is new tissue created after a wound?
- proliferation and differentiation
- fibroblasts are stimulated to divide and secrete ECM components
How do macrophages help with new tissue creation after a wound?
- macrophages send out signals that trigger new blood vessel growth (angiogenesis)
What is epithelialization?
creation of new epithelial tissue
What is maturation (third stage after healing from a wound)?
- decrease in cellularity
- decrease in vascularization
- ECM becomes thinner and altered in organization
- remodeling
What causes scar formation?
due to extensive damage, disorganized epithelia/CT tissues lacking differentiated structural features of original tissue
What are the two main functions of cartilage
- provide a resilient but pliable support structure
- direct the formation and growth of bone
What are chondrocytes?
- secrete collagen and proteoglycan
- make cartilage matrix and tissue
- become entombed (after secreting) called lacuna
- can generate daughter cells in their lacuna and eventually become entombed in their own lacuna
What is appositional growth?
Growth of cartilage upward
What is interstitial growth?
Growth of cartilage in the matrix by chondrocytes
What do chondrocytes arise from?
undifferentiated mesenchymal cells or fibroblasts of the perichondrium generates new chondrocytes during growth
What is the perichondrium?
external layer of connective tissue that surrounds the cartilage
Is cartilage vascularized?
no
What are the functions of hyaline cartilage?
- allows metabolites to diffuse through the tissue
- promotes resiliency to compression forces during joint movement
- allows growth of chondrocytes and matrix from within the matrix
- during growth, it can calcify and attract cells that initiate bone formation
What is elastic cartilage?
has abundant elastic fibers and interconnecting sheets (lamellae) of elastic material (e.g. ear)
What is fibrocartilage?
dense regular connective tissue that is where tendons attach to bones and intervertebral discs
What are osteoprogenitors?
- stem cells capable of cell division to generate osteoblasts and osteocytes
What are osteoblasts?
- line inner layers of both periosteal and end-steal surfaces (where bone growth or remodeling is occurring)
- secrete initial un-mineralized extracellular matrix of bone (osteoid)
- pinch off membrane-enclosed vesicles (matrix vesicles) containing enzymes that initiate bone calcification
What are osteocytes?
- osteoblasts that get encased in the lacuna
- withdraw from cell cycle and minimal secretory function
- extend long processes through tiny channels (canaliculi) that allow them to communicate
- processes form gap junctions with processes from other osteocytes
What is the main function of osteocytes?
monitor bone function (e.g. break) that then they signal
What are osteoclasts?
- degrade bone or cartilage matrix
What critical roles in bone dynamics do osteoclasts play?
- degrade cartilage or bone matrix to allow inward growth of blood vessels during bone formation
- send signals for angiogenesis (blood vessel formation) and nerve growth
- function to resorb already made bone to promote remodeling of the bone matrix
- resorb bone for the purpose of mobilizing Ca2+ into the bloodstream (need proper concentration)
- can recruit osteoprogenitors and MSCs
What is hydroxyapatite?
crystalized form of Ca2+ and PO4 that makes up bone
What are Haversian canals?
channels containing blood vessels and nerves that traverse the long axis through compact bone
What kind of bones does intramembranous ossification form?
- flat bones
What is intramembranous ossification?
- no pre-made cartilage tissue
- groups of mesenchymal cells come together and transform into osteoprogenitors and then differentiate into osteoblasts
- appositional growth
What is endochondral ossification?
- form first by cartilage then transformed into bone over time
- form long bones
What is the appositional growth of endochondral ossification?
- growth and surface
- perichondrium at the cartilage surface, mesenchymal and/or fibroblast like cells proliferate and differentiate into more chondrocytes -> secrete more hyaline matrix
How is cartilage replaced by bone?
- mesenchymal cells -> osteoprogenitors -> osteoblasts (perichondrium is transformed into a periosteum)
- chondrocytes enlarge (hydertrophy) and the cartilage matrix becomes calcified
- osteoclasts are recruited to the region and degrade the calcified cartilage matrix (bring blood vessels, nerves, etc) (interstitial growth
What is the epiphyseal plate?
the only region of proliferative cartilage that remains beneath the epiphyseal ossification regions (at the two epiphyseal ends)
How do long bones continue to grow in length?
- at epiphyseal plate
- promotes continued endochondral ossification
- continued interstitial growth of chondrocytes in their lacunae in the direction of the long axis of the bone
Why does bone growth stop at the epiphyseal growth plate?
when proliferation of the cartilage stops
What is the articular cartilage?
- a sheath of non-proliferative cartilage that remains at the very end (articular surfaces) of the epiphysis
How do bones grow in diameter?
only by appositional growth
- occurs at outer surface of the bone in the periosteum
How is bone remodeling achieved (broadly)?
osteoclast activity is tied to osteoblasts
What are short range signals (morphagens) that regulate bone remodeling?
- TGFbeta (BMPs)
- Wnts
- Notch
- Sonic Hh
- FGF
What are long range signals that regulate bone remodeling?
mostly hormones
- parathyroid hormone (calcium release) activate osteoclasts
- calcitonin (calcium deposition) activate osteoblasts
