Connective Tissue Flashcards
Mesenchymal cells
precursors of all connective tissues. Primarily function in embryogenesis, small number may persist through adulthood to function as stem cells for generation of new connective tissues
Fibroblasts
pre-eminent cells of most connective tissues. Not really a single cell type, look similar histologically but express different markers and proteins in different tissues
myofibroblasts
derive from fibroblast, capable of smooth muscle-like function, in connective tissue that need contractile function, generated at sites of wounds to retract and shrink scar tissue
Adipocytes
derivatives of fibroblasts and/or primitive mesenchymal cells. Main type in adults functions in fat storage, tissues with this are celled white fat. In new borns and children, mitochondria can convert fatty acids to heat, known as brown fat.
Osteoblsts and osteocytes
make bone
chondrocytes
make cartilage, arise from primitive mesenchymal cells. Can also arise from perichondrium once cartilage is formed. Reside in isolated lacuna after release of cartialge ECM. Proliferative are called chondroblasts.
some smooth muscle cells
In walls of blood vessels, make some ECM components, derive from came precursors as other connective tissue.
components of ECM
structual fibers providing mechanical strength and resiliency (collagen and elastin), hydrated gelatinous material (aka ground substances) in which fibers are enmeshed, and numerous other components (GAGs, proteins, solutes)
ground substances
made of proteoglycans, secreted proteins and glycoproteins, inorganic and small organic solutes, and water
Proteoglycans
contain core protein attached to GAGs, with GAGs making up 95% of mass, 3 properties of GAGs relevant to function: 1) high negative charge, highly hydrophilic. 2) rigid extended structures that form gels, promote hydration to allow diffusion of small but inhibit large (bacteria), selective filters due to pore size, large swelling (turgor) pressure to resist large compression force. 3) some proteoglycans can bind and inactivate or activate other proteins (ie growth factors and ECM mod enzymes)
proteins and glygoproteins
proteases that produce collagen and other types of proteins, including growth factors and other polypeptide ligands involved in cell signaling, some will bind and regulate proteoglycans in ECM
structual relationships
CTs always found next to basal surface of spithelia, surrounds muscles and nerves in distinct patterns, surround blood vessels, and surrounds and courses through all organs
Collagen
most abundant structual fibers in ECM, all have similar primary sequence, form fibers of varying size and organization, collagen can be crosslinked w/ other collagen forming higher order structures. Each polypeptide is called an alpha chain consisting of 3 intertwined polypeptide chains to form a rigid tope-like triple helix
Fibrillar collagen
collagen molecules assemble in large bundles called fibrils, collagen is aligned head to tail to create length (several 100 um long) and are stacked for thickness. Have great strength and resist tensile stresses in tissue. Display characteristic banding pattern. formed by type I collagen
Fibril-associated collagen
decorate surfaces of collagen fibrils, thought to link collagen fibrils to each other or tissues
Network-forming collagen
form very thin fibers, interlace to form porous sheets, found in basal laminae, anchoring fibers that attach basal lamina and cells to ECM, some function as filtration barriers (kidneys). Collagen type IV is a common component
collagen synthesis and mod
intracellularly, secreted, further modified extracellularly, made by cells of connective tissue family, synthesized in ER and translocated to ER lumen. Post-translational mods (glycosylated and hydroxylated), assembled into triple helix. Extracellularly N- and C-termini are cleaved, N-termini frags called N-telo peptides, clinically important as levels in urine and blood used to dianose connective tissue and bone disease. Release initiates formation of bundles and end-to-end polymers.
elastic fibers
found in CTs that need distensibility and resiliency, includes elastin and fibrillin, assemble into fibers and sheets. Elastin - filamentous, predominantly random coil conformation, can be stretched, secreted by fibroblasts (like collagen), elastin networks are interwoven with fibrillin, which help organize elastin elements.
CT diversity
mature fibroblasts in different locations look similar (flat spindle shaped cells in most CTs), but produce widely varient ECM in different regions.
CT and tissue injury
wound occurs => release blood platelets into CT => activates blood clots => CT fibroblasts mast cells and other blood cells like macrophages release signaling compounds => increase water permeability of capillary endothelia (swelling), increase cellular permiability to bring in monocytes lymphcytes adn other blood cells, white cells come in (chemotaxis), and finally proliferation of fibroblasts and differentiation of monocytes to macrophages
Histamine
released by mast cells, thought to promote endothelial permeabilization
cytokines
secreted by white blood cell derivatives and fibroblasts, promote several processes of wound response. Also stimulate hematopoietic tissue to stimulate production of more white blood cells
New tissue formation
fibroblasts stimulated to divide and secrete ECM, divistion and differentiation of epithelial stem cells and muscle stem cells. Macrophages trigger angiogenesis, repair, and remodeling
tissue remodeling
cell density reduced, ECM thinner altered in organization, with extensive damage remodeling is imperfect leading to scar tissue
cartilage
2 functions: 1) provide resilient but pliable support, 2) direct formation and growth of bone. In fetus large segments of skeleton are cartilage, by adulthood only articular surfaces bones retain cartilage tissue. Appositional (at perichondrium) and interstitial (middle of bones)
3 types of cartilage
hyaline cartilage, elastic cartilage, and fibrocartilage
Hyaline cartilage
contains collagen forming thin fibrils in an irregular three dimensional pattern, ground substance is rich in proteoglycans and hyaluronic acid (free GAG), promotes hydration and flexibility. Allows metabolites to diffuse through tissue, promotes resiliency to compression and joint movement, allows growth of chondrocytes, and it can calcify to attract cell that initiate bone formation
Elastic cartilage
contains thin collagen fibrils and proteoglycans that is distinguished by abundant elastic fibers and lamellae of elastic material, found in ear epiglottis and larynx, designed for flexibility, does not calcify
Fibrocartilage
contains large bundles of regularly arranged collagen similarly dense to regular CTs, found in continuation of dense reg CTs where tendons attach to bone, and in intervertebral dics. Resists compression and sheer force and joins to bones
osteoprogenitor
stem cells capable of generating osteoblasts and osteocytes. Persistent in periosteal and endosteal surfaces and in soft connective tissue of the channels
Osteoblasts
line inner laters of periosteal and endosteal surfaces where bone growth or remodeling is occuring, secrete osteoid (unmineralized ECM of bone), pinch off matrix vesicles containing calcification enzymes, connected to each other and osteocytes via gap junction, capable of cell division
Osteocytes
derived from osteoblasts, form when surrounded and encased by bone matrix in lacuna, do not divide, extend long processes through canaliculi in calcified matrix, processes form gap junctions, retain limited ability to modify bone matrix, most likely role in bone maintenance is through signaling
Osteoclasts
derived from monocytes in blood (hematopoietic stem cells), related to macrophages, phagocytic, degrade bone or cartilage matrix to allow inward growth of blood vessels during bone formation, resorb made one to promote remodeling, resorb to mobilize Ca2+ into bloodstream
bone ECM
calcified w/ dense parallel collagen fibers, proteoglycans and GAGs (negative charge, many bone specific), contains hydroxyapatite [Ca10(PO4)6(OH)2] crystals found on collagen fibers.
intramembranous ossification
absence of premade cartilage => sheet of CTs, mesenchymal cells come together (condensation) => make osteoprogenitors => osteoblasts => secrete osteoid => more osteoblasts => bone islands join => calcification of matrix => blood vessels grow into network of bone => woven bone => remodeling via osteoclasts => compact lamellar or flat bone made
Endochondral ossification
previously made cartilage (hyaline cartilage) => appositional growth (surface) by chondrocytes from perichondrium secreting hyaline matrix => interstitial growth (within bone) by chondrocytes in matrix lacunae secreting ECM (are isogenous groups, or of clonal origin) => osteoprogenitors from perichondrium => osteoblasts make periosteum => chondrocyte hypertrophy and calification of cartilage matrix => osteoclasts recruited => blood vessel growth w/ osteoprogenitors following => osteoclasts create center of ossification deep to diaphysis => calcification continues => 2 new ossifications at epiphyseal ends (epiphyseal plate) => long bone made
remodeling sequence
osteoclasts activated in specific area => bone resorption of older calcified bone => osteoclast activate osteoblast migration and secretion => new osteoblasts too => osteoid released. In mature adult bone this happens at endosteal surface
regulation
mediated by short-range signals such as Bone Morphogenetic Proteins (BMPs). Trigger intracellular protein phosphorylation, can promote chondrogenesis or osteogenesis. Other controls (FGF, notch and Wnt pathways) in fetus and maybe after brith. Also signals from endocrine glands (estrogen and calcium regulation hormones), mechanical stress, and neuronal stimulation
defects in remodeling and disease
Osteoporosis causes defective resorption and increased bone mass. Osteromalacia Rickets causes abnormal increase in uncalcified osteoids by interfering with mineralization
calcium depositing and resorbtion
parathyroid hormone stimulates calcium liberation (bone resorption), calcitonin stimulates calcium uptake into bone. Hormones control osteoclasts and osteoblasts. Vitamin D is important for calcium uptake from the intestine
