What types of tissue are cartilage and bone considered?
specialized types of connective tissue
True or false: There are more cells than ECM in cartilage and bone.
False. There is more ECM than cells in cartilage and bone.
What resident cells in cartilage are responsible for its production? What cells have the same function in bone?
What are the 2 main components of the ECM of cartilage and bone? What makes them special?
collagen fibers and GAGs (as is true for all connective tissues) but these components are arranged in such a way that makes cartilage and bone well suited to their skeletal functions
What type of embryonic connective tissue are cartilage and bone originated from?
mesenchymal connective tissue
What are the 3 types of cartilage? Generally, how do they differ?
4. largely differ in the fiber content of their matrix
True or false: Cartilage is avascular and aneural.
True. Nutrients and wastes are supplied/taken away via diffusion. Pain in joints due to cartilage damage occurs in surrounding tissues.
What are characteristics of hyaline cartilage? (location, function, composition)
- embryonic skeleton
- costo-chondral junctions (junction btwn costal cartilage of ribs and sternum)
- articular surfaces of synovial joints
- external ear
- supporting structures: trachea, nose
- eustacian tube (links nasopharynx to middle ear)
- epiphyseal plates
- resist compression
- provide smooth surfaces for articulation at diarthrodial joints
- Collagens: primarily type II collagen but also minor amounts of types VI, IX, X, and XI which fxn to crosslink collagenous and non-collagenous components of the ECM
- aggrecan: rich in chroitin sulfate and keratan sulfate
- chondronectin: glycoprotein that mediates adherence of chondrocytes to type II collagen
- growth factors
What are lacunae?
small cavities containing chondrocytes
What are the territorial and interterritorial matrices (in cartilage)? What are the differences in their affinity for basophilic staining?
territorial matrix: matrix surrounding a group of chondrocytes (lacunae)
interterritorial matrix: matrix btwn chondrocytes in a lacunae
territorial matrix is slightly more basophilic (stains darker purple)
What are isogenous groups (in cartilage)?
groups of 2-8 cells in one lacuna suggesting that a cell has divided but daughter cells have not yet produced sufficient matrix to be separated
What is the perichondrium in cartilage?
cellular dense connective tissue layer containing stem cells that produces chondrocytes and ECM.
True or false: Articular surfaces of joint cartilage contain a perichondrium.
False. They do not contain a perichondrium which accounts for the poor capacity of articular cartilage to repair after injury (think of OA)
What are the 2 forms of cartilage growth and how do they differ?
interstitial growth: occurs from within cartilage by mitotic division of chondrocytes and expansion of the flexible matrix
appostional growth: growth by maturation of chondroprogentiors in the perichondrium and formation of new matrix below the perichondrium
What are the characteristics of elastic cartilage? (location, function, composition). What type of stain is used to identify it and why?
- pinna of ear
- internal and external auditory tubes
is similar in appearance to hyaline cartilage with H&E staining. dense bundles of elastic fibers must be visualized with Orcein/Weigert staining. elastic fibers allow for deformability and resilience
What is fibrocartilage? (location, function, composition)
- intervertebral discs
- pubic symphysis
- tendon insertions of bone
is similar in structure of hyaline cartilage only with a dense network of collagen type I (stains with eosin) that is produced by fibroblasts within cartilage. looks very much like dense regular connective tissue with differences in lacunar arrangements and fiber arrays that are sometimes pinnate rather than linear in organization
What are the ways in which bone differs from cartilage?
- is mineralized (with exception of mineralization of hyaline cartilage in endochondral ossification and fibrocartilage during bone repair)
- highly vascular
- has nervous supply
- dynamic: able to remodel and repair itself. does so ~ every ten years
- is interactive with other tissues: produces hormones, growth factors to act on other cells
What are the functions of bone?
- protection to vital tissues/organs
- locomotion: tendon and ligament attachments
- mineral deposition (calcium and phospate homeostasis). its ability to remodel allows it to play role in mineral homeostasis
- stroma for hematopoiesis
Bone has both an organic and inorganic matrix. Describe the compositions of each.
Organic: Type I collagen, aggrecan composites (GAGs and proteoglycans)
inorganic: hydroxyapatite (calcium phosphate)
collagen type I and mineral are the major compositions of bone
What are the 3 main cell types in bone? (just list them)
What are the main features of osteoblasts? (derivation, location, function)
- derived from primitive osteoprogenitor cells (which are derived from mesenchymal stem cells)
- located on internal bone surfaces and beneath the periosteum
- secrete organic bone matrix called osteoid which when mineralized, becomes bone
- become osteocytes when surrounded by a mineralized matrix
What are the main features of osteocytes? (derivation, location, function)
mature bone cells (matured osteoblasts) that reside in lacunae surrounded by bone matrix that they have produced. are deeper in bone than osteoblasts (which reside at surface). send extensive spiderlike cytoplasmic processes into tiny canaliculi in the matrix (canaliculi are microscopic canals btwn lacunae of ossified bone. radiate like wheel spokes from each lacunae to connect with canaliculi of adjacent lacunae and with the Haversian canal). communicate with other osteocytes via gap junctions btwn cytoplasmic processes-forms a cell network within the bone. function in turnover and maintenance of bone maintenance through mechanotransduction: sense mechanical stress on bone and can send signals to osteoblasts to proliferate. also fxn in immobilized osteoporosis. their ability to remove caclium (osteocytic osteolysis) from bony matrix makes them key players in Ca2+ homeostasis.
What are the main features of osteoclasts? How are they stimulated and inhibited? (derivation, location, function)
developed from pluripotent hematopoietic cells that traveled to bone. specialized type of macrophage. multinucleated (up to 200, at least 3-8) large cells (20-100 µm) formed from fusion of monocytes. function in bone resporption by attaching to bony surface through cell membrane integrins and removing inorganic matrix and digesting organic matrix. found in Howship's lacunae that they have created in trabecular surgace of spongy bone or may be active in resorption cavities within compact bone
osteoclast development from monocytes is stimulated by both cytokines (M-CSF and RANKL) and direct interaction with osteoblasts. PTH activity through osteoblasts stimulates osteoclast activity. osteoclasts are directly inhibited through binding of calcitonin.
define the following terms:
- epiphysis: head of a long bone
- diaphysis: long shaft part of bone
- metaphysis: region that connects epiphysis and diaphysis
- epiphyseal line: also known as growth plate. is cartilaginous
- periosteum: dense lining outside of bone
- osteogenic layer: inner cellular layer of periosteum that can give rise to new bone on the outside
- endosteum: single layer of osteogenic cells lining the marrow cavity
True or false: The epiphysis of bone typically contains articular cartilage.
What are the two types of bone marrow?
red marrow: hematopoietic
yellow marrow: is more fatty. increases with age.
What are the 2 types of bone? (just list them). How may they be further classifed by maturity?
spongy aka trabecular, alveolar, cancellous
compact aka lamellar, Haversian, cortical, compacta
woven: immature. not very well organized
lamellar: mature. is well organized
What are characteristics of spongy (aka trabecular, alveolar, cancellous) bone? What is it composed of?
interconnected network of trabeculae or bone spicules that provide a supporting framework beneath or above compact bone. can remodel in response to stress. marrow permeates the space btwn bone spicules.
trabeculae contain entrapped osteocytes. a layer of osteoblasts cover the surface and produce a layer of organic matrix called the osteoid on teh surface of mineralized trabeculae. a similar layer of cells on the inner surface of the marrow cavity forms the endosteum (contains osteogenic cells)
True or false: Since trabeculae (in spongy bone) are thin and surrounded by capillaries of the marrow cavity, osteocytes are nourished by diffusion from the surface through canalicular channels.
What are characteristics of compact (aka lamellar, Haversian, cortical, compacta) bone? What is it composed of?
dense outer subunits of bone consisting of calcified layers arranged in concentric layers of lamellae (osteons, Haversian systems) around a core of vessels and nerves. may lack regular Haversian systems in woven bone (immature bone)
more detail about above:
Haversian systems/osteons are organized around Haversian canals which contain a neurovascular bundle conisiting of an artery, a vein, and a nerve.
Volkmann's canal: interconnect Haversian canals. are perpendicular to the longitudinal axis of osteons
when picturing a step ladder, can think of Haversian canals as long sides of step ladder and Volkmann's canals as the steps
osteoclasts: can be found periodically on trabecullar surface or in erosion pits called Howship's lacunae. attachments at their perimeter and ruffled border at the bony surface create an acidic microenvironment for demineralization and lysosomal digestion of organic matrix
What are resporption cavities? What types of cells do they contain and how do those cells function in resorption cavities?
resorption cavites are sites of bone removal that create larger spaces intersecting the boundaries of osteons. these cavities are often cross sections of tunnels called cutting cones in which osteoclasts spearhead bone removal at the tip of the cone. attach to bone at their perimeter and ruffled border. release H+ (creates acidic environment) to break down mineral and proteases to break down organic components. attach to bones via integrins (heterodimeric calcium dependent integral membrane cellular adhesion proteins)
What are primary and secondary lamellae? What do they come from?
after osteoclast activity, new osteons are produced by laying down bone within previous sites of erosion so that the lamellae are laid down the outside in with the newest lamellae immediately surrounding the Haversian canal and the oldest at the perimeter. lamella of complete osteons are called primary lamellae. if lamellae are partially eroded, they presist as residual or secondary lamellae btwn fully formed primary osteons.
Bone can only grow by a. interstitial or b. appositional growth. What is the reason for this?
b. appositional growth bc matrix cannot expand from within
What are the 2 main modes of bone growth? (just list)
endochondral ossification: bone is formed on an existing cartilage template
intramembranous bone formation/ossification: bone is laid down directly without cartilage step
How does intramembranous bone formation/ossification take place? (where in the body, what cells are involved)
bone formation in dense connective tissue membranes (flat bones of the skull, shaft of long bones). osteoprogenitor cells differentiate from mesenchymal stem cells and being to mineralized their surrounding matrix to form bone. process of osteoprogenitor differentiation to osteoblast and osteoblast secretion of inorganic matrix (osteoid) is regulated by a variety of growth factors and hormones such as bone morphogenic progeins, IGF-1, Wnt proteins, etc.
How does endochondral ossification take place? Discuss this along with growth of the epiphyseal plate. Talk about where this happens in the body.
endochondral ossification takes place in fetal bones and in the growing epiphyses of long bones. is replacing of cartilage with bone. cartilage model provides a flexible structure for growth (interstitial and appositional) and remodeling of the immature skeleton.
growth of epiphyseal plate: chondrocytes in deeper layers of epiphyseal cartilage can proliferate to produce elongation of bone. as new cells are produced, however, they proceed on a program that leads to their replacement by bone. the steps occur in a series of zones as follows (epiphysis to diaphysis):
zone of reserve cartilage
zone of proliferation: chondrocytes reproduce. where growth takes place
zone of hypertrophy: cells begin to die
zone of calcified cartilage: dead cells become calcified
zone of vascular invasion, bone deposition, and resorption: where endochondral ossification takes place. causes longitudinal growth. osteoblasts in the marrow cavity lay down bone on residual calcified cartilage
What factors are implicated in the growth of the epiphyseal plate?
genetics, hormones, growth factors (excess growth hormone leading to IGF-1 and somatomedin excess causes acromegaly). cartilage hypertrophy and death is also regulated by hormones and factors such as thyroid hormone.
Discuss the invasion of blood vessels in bone and how this relates to primary and secondary centers of ossification.
Primary centers of ossification are formed from initial invasion of blood vessels. secondary centers of ossification are formed above the epiphyseal growth plate from secondary invasion of blood vessels (occurs a little later in life). secondary centers of ossification are a prelude to the cessation of growth during whic the entire growth plate is replaced with bone. steps in bone growth in secondary center of ossification are the same as in primary center of ossification: cartilage death, calcification of cartilage matrix, invasion by blood vessels that brings in osteogenic cells, then bone formation within cartilage model
What hormone stimulates fusion of the epiphyseal growth plate?
Discuss what occurs in bone fracture repair.
Fibrin in the blood clot at the fracture site first produces a scaffold for organization of fibroblasts as in a scar. These generate a cartilaginous callus or union. The soft callus undergoes a transformation (same as occurs in ossification-cartilage death, calcification of cartilage matrix, invasion of blood vessels that bring in osteogenic cells, bone formation) to a vascularized bony callus. subsequent remodeling can make the fracture site grossly indistinguishable from orininal bone if fracture is properly reduced. see slide 46 of notes for visual
What is osteoarthritis?
characterized by chondrocyte death and loss of joint cartilage, inflammation of synovial membranes, narrowing of joint space, thinckened subchondral bone, and development of osteophytes (disease of whole joint). result is a painful non-functioning joint. pain comes from surrounding tissue: bone, synovial membrane (cartilage is avascular)
What is osteoporosis? (cells and factors involved)
porous bones. decreased bone mass related to:
-decrease in estrogen and decreased bone matrix formation (reason for increased risk of osteoporosis in post-menopausal women bc stop actively making estrogen. estrogen comes from aromatase coversion of androgens to estrogens)
decreased vitamin D and calcium absorption in alcoholic cirrhosis
decreased vitamin D, hypercalcemia, and secondary hyperparathyroidism in renal disease
trabecular areas are more susceptible
age related but is also pathological
Paget's disease (cells involved, cause, exam finding)
skeletal disorder associated with thickening and weakening of bones related to disregulation of osteoclastic and osteoblastic activity. have excessive bone turnover and have mostly woven (immature) bone-weaker bones. turnover is localized and area of skin is warm due to cellular activity. etiology is unknown but may be viral
What is osteomalacia? What is this disease called in children (when skeleton is still growing)?
group of disorders characterized by failure to form normal mineralized matrix-excessive osteoid presence-soft bone. is called Ricket's disease in children. due to Vitamin D deficiency.
characterized by hypermineralization of bones. bones are very dense and results in mechanically incompetent limbs
What is osteogenesis imperfecta?
group of inherited disorders due to mutation in type I collagen. can be null allele mutation (Type I, least severe type) or structural mutations (typically substiution of glycine, results in more severe forms-Type II (lethal), Types II and IV). thin delicate bones, short stature, multiple fractures