Histology of Connective Tissue, Cartilage, and Bone Flashcards
Connective tissue components
Cells, fibers, ECM
Extracellular matrix components
AKA ground substance, collagens, noncollagenous glycoproteins, proteoglycans
Connective tissue resident cell
Fibroblast
Fibroblast function
Production and maintenance of the ECM
Connective tissue immigrant cells
Macrophages, mast cells, plasma cells
Connective tissue roles
Immune and inflammatory responses, tissue repair after injury
Types of connective tissue proper
Loose CT, Dense CT
Types of dense connective tissue
Dense regular, dense irregular
Types of specialized connective tissue
Hematopoietic tissue, adipose tissue, cartilage, bone
Loose connective tissue
Contains more cells than collagen fibers, found surrounding blood vessels, nerves, muscles
Dense connective tissue
Contains more collagen fibers than cells, can be regular or irregular, poorly vascularized
Dense regular connective tissue
Collagen fibers are preferentially oriented, found in tendons, ligaments, cornea
Dense irregular connective tissue
Collagen fibers are randomly oriented, found in the dermis of the skin and walls of the intestine
Glycosaminoglycans
AKA GAGs, long unbranched polysaccharides consisting of repeating disaccharide units, highly negatively charged, associate with larger amounts of water to make hydrated gels
Examples of GAGs
Hyaluronic acid, dermatan sulfate, chondriotin sulfate, herparin, heparan sulfate, keratan sulfate
Proteoglycans
Composed of a protein core to which at least one glycosaminoglycan is covalently bound, highly negatively charged and help to organize and stabilize the matrix through interactions with other molecules, can also create a barrier to the passage of positively charged molecules into the basal lamina of epithelial cells
Examples of proteoglycans
Decorin, aggrecan
Adhesive glycoproteins
Help to facilitate the attachment of cells to the ECM, affect the growth, survival, morphology, differentiation and motility of cells, consist of disulfide-bonded subunits with binding sites
Examples of glycoproteins
Laminin, fibronectin
Collagen
Most abundant protein, types I, II, III are the most abundant, form fibrils of similar structure to provide tensile strength to tissues, made up of the collagen alpha chains that associate in a right-handed triple helix (every third amino acid is glycine), these molecules then associate with each other to form collagen fibers
Formation of collagen by fibroblasts
Translation of the alpha-chain mRNA in the RER to individual alpha-chains that are modified by glycosylation and hydroxylation, alpha-chains assemble into triple helix with non-helical ends called pro-peptides, these form the soluble procollogen molecule, which is then secreted from the cell into the extracellular space and cleaved by proteases to make insoluble tropocollagen molecules that spontaneously assemble into collagen fibrils, these then associate with each other to form collagen fibers and are crosslinked by lysyl oxidase and mature collagen fibers are formed
Types of cartilage
Hyaline, elastic, fibrous
Cartilage
Consists of chrondrocytes embedded in ECM, usually surrounded by perichondrium, avascular, nutrition through the ECM, modest repair capacity
Perichondrium
Contains stem cells that differentiate into chondroblasts that give rise to chondrocytes
Cartilage mechanisms of growth
Interstitial growth by division of existing chondrocytes within the cartilage, or appositional growth by the production of new chondroblasts and chondrocytes at the surface of the cartilage by stem cells from the perichondrium
Hyaline cartilage
Avascular, poor healing capabilities, surrounded by perichondrium, contains type II collagen, proteoglycans and water, water is what provides the compressive strength of hyaline, found in skeleton of embryo, articular cartilage in joints, cartilage of respiratory tract
Elastic cartilage
Avascular, heals poorly, surrounded by perichondrium, contains type II collagen, proteoglycans, and elastic fibers, found in external ear and epiglottis
Fibrous cartilage
Avascular, heals poorly, no perichondrium, contains type I collagen, resembles dense fibrous CT, found in intervertebral discs, menisci of the knee, pubic symphysis
Bone
Rigid, inflexible CT with ECM that has been mineralized by salts of calcium and phosphate, high vascularized and metabolically very active, constantly being remodeled and reshaped in response to physical stress and mineral needs of the body
Functions of bone
Provide attachment sites for muscles, protect the soft tissue organs, serve as a reservoir for calcium and phosphate ions
Organic component of bone ECM
Osteoid, contains type I collagen, proteoglycans, noncollagenous glycoproteins (osteocalcin, osteopontin, osteonectin)
Inorganic component of bone ECM
Bone mineral, contains hydroxyapatite, where 99% of the body’s store of calcium ions are found, contribute to the strength and rigidity of bone
Major cell types of bone
Osteoblasts, osteocytes, osteoclasts, osteoprogenitor cells
Osteoblast
Derived from osteoprogenitor cells, main bone-forming cells, actively deposit osteoid along the osteoblast-bone interface, initiate and control the mineralization of the osteoid, has extensive RER
Osteoblast proteins expressed
PTH receptor, alkaline phosphatase, vitamin D3, IGF-1 receptor, type I collagen, osteocalcin, osteopontin, osteoprotegerin, RANKL
Parathyroid hormone receptor
Stimulation of the receptor by PTH induces RANKL and mCSF expression and inhibits OPG production by osteoblast
Alkaline phosphatase
Cell surface enzyme that produces high levels of phosphate ion during bone matrix synthesis, important metabolic marker of bone formation
Vitamin D3
Regulates expression of osteocalcin, a protein with high bonding affinity for hydroxyapatite
IGF-1 receptor
Binds IGF-1 produced by the liver and stimulates the growth of the long bone and osteoid production
Type I collagen
Major component of the osteoid matrix
Osteocalcin
Non-collagenous protein required for bone mineralization
Osteopontin
Non-collagenous protein that mediates the interaction of osteoclasts with the bone surface
Osteoprotegerin
AKA OPG, non-collagenous protein that functions as a decoy receptor for the RANKL and inhibits osteoclastogenesis
RANKL
Ligand for the RANK receptor on osteoclast precursors and a receptor for OPG
Woven bone
AKA primary bone, first bone matrix produced by osteoblasts, matrix contains loose, randomly oreinted collagen fibers and low amounts of hydroxyapatite
Lamellar bone
AKA secondary bone, woven bone that has been remodeled, matrix contains organized sheets of collagen fibers and high amounts of hydroxyapatite
Osteocyte
Flattened out and transformed osteoblasts, embedded in the mineralized bone matrix, highly branched cells with their body occupying lacunae within the layers of the bone matrix, canaliculi course through the bone matrix to interconnect neighboring lacunae and form gap junctions between adjacent cells, extracellular fluid containing nutrients diffuse through canaliculi to support osteocytes, osteocytes respond to forces on the bone and release factors to stimulate bone remodeling or turnover
Osteoclast
Large, multinucleated cells, function to degrade bone matrix, derived from monocyte precursors in the bone marrow, transformation occurs by a process known as osteoclastogenesis, highly polarized when active with a shallow concavity in the bone surface, contains high levels of carbonic anhydrase II
Osteoclastogenesis
Monocyte from bone marrow expresses M-CSF receptor on the surface, becomes a macrophage, M-CSF ligand from osteoblast binds receptor and induces RANK expression for its ligand RANKL that is expressed on the surface of osteoblasts, which it binds to commit the cell to osteoclastogenesis, becomes a multinucleated osteoclast precursor, can be inhibited by OPG which blocks the binding of RANKL to RANK, so osteoblasts control osteoclast differentiation, a resting osteoclast uncouples from the osteoblast and the maturation is complete when the sealing zone and ruffled border appear
Resorption pit
AKA Howship’s lacuna, shallow concavity in the bone surface that associates with the active osteoclast
Carbonic anhydrase II
Generates high levels of hydrogen ions from CO2 and water to create an acidic microenvironment needed to solubilize the mineralized component of bone
Bicarbonate
Generated during the solubilizing of bone, exchanged for chloride ions at the apical surface of osteoclasts to prevent excessive rise in intracellular pH
Chloride ions in Howship’s lacuna
Chloride ions are transported in by chloride channels at the basal surface of the cells following exchange for bicarbonate
Cathepsin K and matrix metalloprotease 9
Proteases released into resorption pit to degrade the organic matrix following solubilization of the mineral components of the bone by acidification
Calcitonin
Released by the thyroid gland in response to high plasma calcium levels, when bound inhibits activity of osteoclast and causes its release from the bone surface
Cortical bone
AKA compact bone, osteocytes present in lacunae and the bone matrix are arranged into osteons that contain a Haversian canal surrounded by 4-10 concentric layers (lamellae) of bone matrix, canaliculi seen traversing lamellae to form connections among lacunae and central canals, blood vessels are present in the center of Haversian canals, osteons are being continuously remodeled
Trabecular bone
AKA cancellous bone, contains layers of lamellae that form the bony trabeculae that project into the marrow cavity, no osteons, osteocytes are interspersed randomly throughout trabeculae and in growing bone, trabeculae usually covered with osteoblasts and osteoclasts
Calcium homeostasis
Mechanisms by which the body maintains adequate calcium levels in order to prevent hypercalcemia or hypocalcemia, appropriate calcium levels are important for glandular secretion, muscle contraction, and neuronal function, regulated by osteoblasts and osteoclasts
Hypocalcemia response
Parathyroid gland secretes PTH to decrease excretion and increase absorption in the kidney and gut, and activates osteoblast receptors to decrease osteoid matrix synthesis, osteoclast activating factors are released and osteoclasts differentiate to increase bone turnover and increase plasma calcium levels
Hypercalcemia response
Thyroid gland secretes calcitonin and increases excretion and decreases absorption in the kidney and gut, osteoclast calcitonin receptors (CTR) are activated and osteoclast is inactivated and retracted away from the bone surface to decrease bone turnover, and plasma calcium levels are decreased