Skeletal System Flashcards
Cartilage
A specialized connective tissue
Cartilage 3 functions
Support & framework: embryonic skeleton (bone growth), airways
Shock absorption, resisting compression: intervertabral disks, menisci, pubic symphysis
Smooth gliding surfaces: Articular surfaces of bones within joints
3 cartilages of the body
Hyaline cartilage
Fibrocartilage
Elastic cartilage
Chondrocytes
Cells responsible for synthesis of cartilage-specific ECM components
Chondroblasts
Chondrocyte precursors capable of forming a cartilage-specific ECM, but not yet encased within the matrix
Ultrastructure
Typical of a cell actively producing proteins
Abundant RER - collagen
Prominent Golgi complexes - proteoglycans
Chondrocyte lineage*
Originate from mesenchymal stem cells, which can also give rise to osteoblasts (bone), myoblasts (muscle), and adipocytes (fat)
Transcription factor Sox9 required for expression of cartilage-specific ECM (collagen type II)
Lack of Sox9 expression prevents chondrogenic differentiate from mesenchymal progenitor cells
Cartilage ECM*
Ground substance: ECM contains large proteoglycan aggregates like aggrecan, that interact with collagen
GAGs: negatively charged chains (chondroitan sulfate and keratan sulfate) on proteoglycans that bind water
Creates a shock absorber bc of its stiffness & elasticity
Cartilage - special characteristics
Avascular
Nutrients and O2 must diffuse through ECM
Limits cartilage growth & repair
Chondrocytes have low metabolic rate & do not require high O2 conc in order to perform normal functions
Perichondrium*
Sheath of dense CT surrounding most cartilage
Contains vasculature, nerves, & lymphatic vessels
Outer layer of fibroblasts
Inner layer of chondroblast precursors (chondrogenic)
Cartilage growth*
Attributed to 2 processes:
Appositional growth: differentiation of perichondrial (chondroblast) cells. Most common way that cartilage increases girth postnatally
Interstitial growth: results from mitotic division of preexisting chondrocytes.
E.g epiphyseal (growth) plate for increasing long bone lengths, articular cartilage regeneration bc it lacks a perichondrium
Hyaline cartilage*
Most common of 3 cartilage types
Locations: articular surfaces of moveable joints, walls of larger respiratory passages (nose, larynx, trachea, bronchi), costal cartilages, & epiphyseal (growth) plates
Fibers: type II collagen
Growth: appositional & interstitial
Articular cartilage - a form of hyaline cartilage*
Covers articular surfaces of bones
Lacks a perichondrium
Diffusion of O2 & nutrients from synovial fluid
Elastic cartilage*
Very similar to hyaline cartilage except contains a large network of fine elastic fibers
Locations: auricle of ear, walls of the external auditory canals, Eustachian tubes, epiglottic
Fibers: type II collagen & elastic fibers
Growth: appositional & interstitial
Fibrocartilage*
Tissue intermediate between dense CY & hyaline cartilage
*on histological sections, border between dense CT & fibrocartilage not clear-cute
Locations: intervertebral discs, attachments of certain ligaments, pubic symphysis, menisci
Fibers; type I collagen & smaller amounts of type II collagen
Growth: interstitial
No distinct perichondrium
Bone
Comprises largest proportion of body’s CT mass
Adult human skeleton has over 200 distinct skeletal elements
Roles of bone
Framework for trunk and extremities to withstand mechanical loads
Levers for locomotor function
Protect vulnerable viscera
skull for the brain
vertebral column for the spinalcord
rib cage for the heart and lungs
Site for hematopoiesis (bone marrow)
Maintain mineral (Ca) homeostasis
3 parts of long bone
Epiphysis (ends)
Metaphysis (beneath growth plate)
Diaphysis (shaft)
What are all of the components of long bone*
3 parts (epiphysis, metaphysis, & diaphysis)
Medullary (marrow) cavity
Endosteum - contains osteoprogenitor cells
Periosteium - membrane around the bone
Fibrous layer
Osteogenic layer
Articular cartilage - hyaline cartilage covers the articulating surfaces of bone
A haversion system is also known as an…*
osteon
Spongy bone
Lamellar but usually not haversion
The cavities of the spongy bone are continuous with the bone marrow cavity of the diaphysis
The endosteum
Consists of osteoprogenitor cells & reticular fibers.
In adults, these cells can become osteoblasts during conditions requiring bone repair, such as bone fracture
The periosteum is formed by 2 layers
The outer layer contains abundant collagen fibers and blood vessels that penetrate Volkmann’s canals
The inner layer contains osteoprogenitor cells
Sharpey’s fibers
Collagen fibers derived from outer layer of periosteum, projecting into the outer circumferential lamellar system
Osteoblasts*
Responsible for synthesis and mineralization of bone ECM
Protein producing cells are cuboidal or columnar and lining active bone-forming surfaces
Osteoid vs mineralized matrix
Osteoblast lineage*
Originate from mesenchymal stem cells (progenitors) which can also give rise to chondrocytes (cartilage), myoblasts (muscle), & adipocyte (fat)
The transcription factor Runx2 (Runt-related transcription factor-2), is required for the expression of bone-specific ECM (collagen type I, osteocalcin and other non-collagenous proteins)
Bone cells: osteocytes*
Terminally differentiated osteobalsts that become encased in the ECM
Make up over 90% of all bone cells
Dendritic processes maintain contact with other osteocytes, Haversian canals, the bone surface (periosteum), & the bone marrow (endosteum) - sites of vasculature
Bone cells: osteoclasts*
Large, multinucleated cells that are responsible for bone resorption/degradation of mineralized bone
Actively resorbing cells sit with Howship’s lacunae
Osteoclasts are derived from hematopoietic stem cells and share a common progenitor with the monocyte/macrophage lineage
Bone cells: osteoclasts*
Large size & multinucleated (polykaryon)
Clear zone (sealing zone)
Ruffled border
Around the circumference of the ruffled border, where the plasma membrane is closely applied to the bone, ______ ______ accumulate to form a _______ _______, together with alphavbeta3 integrin & osteopontin
Around the circumference of the ruffled border, where the plasma membrane is closely applied to the bone, actin filaments accumulate to form a sealing zone together with alphavbeta3 integrin & osteopontin
A chloride channel prevents…
An excessive rise of intracellular pH
______ is exchanged for ______, which is then transported by the chloride channel in the ruffled border to Howship’s lacunae. ____ -_______ exchanger ensures the maintenance of cytoplasmic electroneutrality.
Bicarbone;chloride;bicarbonate-chloride
________ _______ __ generates protons from CO2 & H2O. H+ is released into Howship’s lacuna by an H+-ATPase pump to create an acidic environment (pH -4.5) for solubulizing mineralized bone
Carbonic anhydrate II generates protons from CO2 & H2O. H+ is released into Howship’s lacuna by an H+-ATPase pump to create an acidic environment (pH -4.5) for solubulizing mineralized bone
________ ___ & ______ ________ sre released into Howships’s lacuna to degrade the organic matrix (type I collagen & noncollagenous proteins) following sokubulization of minerals by acidification
Cathepain K & matrix metalloproteinase-9 (MMP-9) are released into Howships’s lacuna to degrade the organic matrix (type I collagen & noncollagenous proteins) following sokubulization of minerals by acidification
Components of osteoclasts
Mitochondria
Coated vesicles
Acidified vesicles
Nucleus
Ruffled border
The osteoclast is a highly polarized cell associated with a…
The osteoclast is a highly polarized cell associated with a shallow concavity, Howship’s lacuna or the subosteoclastic compartment. The surface facing the lacuna displays a ruffled border
Osteoclasts are….
multinucleated cells & contain abundant mitochondria, coated vesicles (with degraded organic bone matrix material) & acidified vesicles (with electrogenic H+-ATPase)
Bone cells - regulatory interactions
A balance of bone formation and resorption is necessary to maintain the structural integrity of the adult skeleton
RANK-L*
Receptor activator of NF-kB (RANK) & its ligand (RANK-L): induces osteoclast formation & activation
Macrophage colony stimulating factor (M-CSF): stimulates early commitment to osteoclast lineage
Osteoprotegerin (OPG): produced by osteoblasts it acts as a RANK-L decoy receptor
Bone has how much of body’s Ca?
99%
Bone has how much of body’s potassium?
4%
Bone has how much of body’s sodium?
35%
Bone has how much of body’s magnesium?
50%
Bone has how much of body’s carbonate?
80%
Bone has how much of body’s phosphate?
99%
At intestine, ______ & ______ ions are absorbed from the diet. The rate of absorption is ______ regulated
At intestine, Ca & phosphate ions are absorbed from the diet. The rate of absorption is hormonally regulated
Within the skeleton, ______ are continuously depositing new bone matrix. At the same time, _____ are eroding existing matrix and releasing ___ & ___ ions that enter circulation
Within the skeleton, osteoblasts are continuously depositing new bone matrix. At the same time, osteoclasts are eroding existing matrix and releasing Ca & phosphate ions that enter circulation
The balance between osteoblast & osteoclast activity is ______ ____
hormonally regulated
At the kidneys…
The levels of Ca and phosphate ions lost in the urine is hormonally regulated
Osteogenesis 2 processes
Intramembranous - bone tissue formed directly in primitive CT (mesenchyme)
Endochondral - Bone tissue replaces a hyaline cartilage template
Intramembranous bone formation
Mesencyme
Bone blastema
Primary bone tissue
Endochondral ossification
Development of the primary ossification center:
Hyaline cartilage is the template of a long bone
Osteoprogenitor cells of perichondrium form periosteal collar
Blood vessels, forming the periosteal bud, branch in opposite directions
Endochondral ossification (talk about the chondrocytes…) - formation center of ossification
Proliferation of chondrocytes followed by their hypertrophy at midpoint of the shaft initiates formation of the primary ossification center
Hypertrophic chondrocytes secrete vascular endothelial cell growth factor to induce sprouting of blood vessels from perichondrium
Then, calcification of the matrix & apoptosis of hypertrophic chondrocytes occur
The epiphyseal cartilaginous growth plate between the metaphysis & epiphysis will eventually…
be replaced by bone. The bone at this site is particularly dense & recognized as an epiphyseal line
The thin cap of cartilage from the original hyaline model remains as…
articular cartilage and prevents bone to bone contact within the joint
Development of secondary ossification center
Blood vessels and osteoprogenitor cells infiltrate epiphysis & secondary ossification is established
A similar secondary ossification center appears in the opposite epiphysis
Epiphyseal plate becomes replaced by an epiphyseal line. This process occurs gradually from puberty to maturity, and the long bone can no longer grow in length
Blood vessels from the diaphysis & epiphysis intercommunicate
All the epiphyseal cartilage is replaced by bone, except for the articular surface
Zones of endochondral ossification
Reserve zone
Proliferative zone
Hypertrophic zone
Vascular invasion zone
Reserve zone
Primitive hyaline cartilage responsible for the growth in length of the bone as erosion and bone deposition advance into this zone
Proliferative zone
Proliferating chondrocytes align as vertical & parallel columns
Contains flattened chondrocytes in columns or clusters parallel to the growth axis
Chondrocytes are separated by the territorial matrix
ALl chondrocytes within a cluster share common territorial matrix
Hypertrophic zone
Apoptosis of chondrocytes and calcification of the territorial matrix
Hypertrophic chondrocytes calcify the matrix, make type X collagen, attract blood vessels by secreting vascular endothelial growth factor, instruct perichondrial cells to become osteoblasts to form bone collar and undergo apoptosis
Vascular invasion zone
Blood vessels penetrate the transverse calcified septa, and carry osteoprogenitor cells with them
Blood vessels penetrate the transverse septa of the last hypertrophic chondrocyte layer & form vascular spaces with blood (lacunae)
Longitudinal septa, corresponding to the interterritorial matrix, are not degraded by the vascular invasion
Osteoblasts beneath the sites of vascular invasion begin to deposit osteoid along longitudinal septa forming trabecular bone
Longitudinal septa at the vascular invasion zones are the…
first sites where osteoblasts begin to deposit bone matrix (osteoid)
Increases in bone diameter result from…
appositional growth
Name all fracture stages
Hematoma formation
Callus formation
Bone remodeling
Hematoma formation & inflammation (within hours)
Pain, warmth, tenderness, & instability
Recruitment & prolif of MSC progenitor populations (periosteum)
Children have thicker + better vascularized periosteum facilitating faster healing
Hematoma formation (low pO2 @ fracture site promotes)
MSC differentiation into chondrocytes, which will produce cartilage
Angiogenesis
Callus formation (soft callus formation)
Development of a fibrous & cartilaginous callus (collar) that surrounds the fracture
Callus progressively widens & stiffens to ultimately immobilize fractured ends of bone
Callus formation (hard callus formation)
Initial bone formation in the callus
Endochondral ossification of cartilage
Intramembranous ossification directly on bone surface
Proportions of ossification processes
Bone remodeling (months to years)
Conversion of immature (woven bone) into mature (lamellar) bone
Haversion systems
reconstituted
Biomechanical forces direct relative amounts of bone deposition
More bone is deposited
in areas of greater
mechanical stress
Osteoporosis (bone loss)
Uncoupling of bone formation & resorption in favor of resorption
Factors include aging, post-menopausal (estrogen-deficiency), disuse inflammation, diabetes, and others
Rickets/osteomalacia
Inadequate mineralization:
Defective vit D intake/metabolism
Defective mineralization of osteoid
Increased osteoid thickness
Increased fracture risk
Treatment by vit D supplementation
Classification of joints by tissue type
Fibrous
Cartilaginous
Synovial
Classification of joints by degree of movement
Synarthrosis - immovable
Cartilaginous - slightly moveable
Synovial - freely moveable
Fibrous joints
Sutures - immoveable; e.g. flat bones of the skull
Gomphoses - immoveable; e.g. teeth articulating with their sockets in maxilla/mandible (periodontal ligament)
Syndesmoses - slightly moveable; e.g. interosseous membrane between radius & ulna
Cartilaginous joints
Synchondroses - bones connected by hyaline cartilage - immoveable; e.g. ribs to sternum & epiphyseal plates
Symphyses - bones united by fibrocartilage - slightly moveable; e.g. pubic symphysis, intervertebral discs
Synovial joints
Defined by the presence of a fluid-filled cavity contained within a fibrous capsule. They are freely moveable & commonly found throughout the body
Structure of synovial joints (components)
Articular cartilage
Joint capsule
Synovial fluid
Functions of synovial fluid
Lubrication
Nutrient distribution
Shock absorption
