CAPS 390: Cartilage and Bone

bone is highly vascularized

- Blood vessels enter the shaft (diaphysis) and the ends (epiphysis) of bone = periosteal buds - Fully developed bone (D) has articular and reserve growth/epiphyseal plate cartilage

Differences Between Cartilage & Bone

- Cartilage ECM is a firm, hydrated, plastic-like gel with a high diffusion index - Bone ECM is solid and mineralized (calcium phosphate) with a low diffusion index - Cartilage is avascular (no blood vessels) - Bone is richly vascularized -After trauma or injury, overall repair and regeneration are much more efficient in bone than in cartilage.

Fibrocartilage

- Matrix contains high amounts of thick, strong Type I collagen fibers = very high tensile strength compared to other type of cartilage - Also has a number of characteristics of dense regular connective tissue with some chondrocytes in lacunae and some proteoglycans's that give some resistance to compression - No distinct perichondrium = very, very low regenerative potential - Found in intervertebral disks, pubic symphysis, and sites of tendon insertion/attachment to bones, cushioning meniscus in some joints (eg. knee cartilage that is often 'torn') - Mesenchymal stem cells can migrate into wounded Hyaline cartilage from bone which can result in the formation of fibrocartilage. Fibrocartilage eventually degenerates (avascular, compressive load) and can be replaced by bone

bone starts out as cartilage...

- bone starts out as cartilage - blood vessels invade the cartilage and make a periosteal bud - cartilage dies away - bone replaces where the cartilage - usually happens in the centre or the shaft of the bone (diaphysis) - secondarily happens at the ends of the bones (epiphysis) - cartilage at the end makes the growth plate

cartilage vs bone: ECM

- cartilage ECM is firm, hydrated, plastic-like gel with a high diffusion index - bone ECM is solid and mineralized (calcium phosphate) with low diffusion index

cartilage vs bone: vascularization

- cartilage is avascular (there are no blood vessels) - bone is richly vascularized

synovial joints: cartilage and bone During development and growth

- chondroprogenitors are in the periosteum - most of the cartilage scaffold gets replaced and becomes bone - at the ends becomes the articular cartilage

Spongy bone

- consists of small conected pieces of bone tissue called 'Spicules' - has osteoblasts - has osteocytes - has osteoclasts

periosteum: outer fibrous layer

- dense irregular connective tissue

What's the problem with a herniated disc?

- doesn't heal well - dealing with this is dealing with inflammation

Nucleus Pulposus

- embryonic remnant of Notochord - very few cells - very high hyaluronic acid and water content - gelatinous - allows disc to compress when weight-bearing and expand again when weight removed

Spongy bone: Osteocytes

- encased in lancuna - lays down mineralized crystals - derived from osteoblasts

alkaline phosphatase

- facilitates deposition by osteoblasts and osteocytes - can enter the bloodstream and therefore is a useful serum marker of bone deposition activty

cartilage

- firm and slippery - important function in long bones: pubertal age kids and younger where there's cartilage in the bones that form growth plates (allows bones to get longer) - reserve cartilage in the bone - Support for soft tissues! - Sliding/Low frictional surfaces in joints! - Growth (epiphyseal) plates of long bones

metalloproteases

- good at chewing up ECM - are secreted at the sealing point - come from hemapoietic stem cells

osteoporosis

- increase in bone porosity (bone loss) -50% incidence in women >50 (metapause) - increased risk of frature - bone remodeling is skewed towards greater resorption (activates osteoclasts)

Spongy bone: Osteoclasts

- large multinucleate cell - derived from hematopoeitic stem cells - can digest/resorb/destroy bone matrix - important for bone remodelling/repair and for controlling blood levels of calcium

periosteum: inner cambium layer

- made up of osteoprogenitors and osteoblasts

formation of fibrocartilaginous repair

- occurs initially in wounded articular cartilage - Mesenchymal Stem Cells (yellow) can migrate from bone into wounded cartilage - Within the wound stem cells differentiate into 'fibro' chondrocytes (more collagen I, less GAG's) - Due to avascularity and compressive load in joint, the fibrocartilage eventually degenerates -Degenerating fibrocartilage is then finally replaced by bone on joint surface = osteoarthritis

osteoclasts do what?

- osteclasts don't make bone, they eat bone - when you have a fracture, they clean it up so that blasts can come in to lay down new bone - Oc also get going when there's not enough blood calcium - hormones that act on the Oc to juice them up or calm them down

Organic component of the ECM of bone

- osteoid - ~35% of dry weight - not all calcium phosphate materials - has little ground substance - unlike cartilage, there's a little PG and GP - PG and GP bind integrins - tons of interwoven collagen I (what makes it pink) - low amount of diffusion -deposited first by osteoblasts

Periosteum

- protective covering on external surface of the bone - comprised of two layers 1. Outer fibrous layer, dense irregular CT 2. Inner cambium layer, osteoprogenitors and osteoblasts -its sharpy fibers (collagen fibers) anchor the periosteum to bone -is a membrane that covers the outer surface of all bones, except at the joints of long bones

roof of the larynx: epiglottis

- rubs a lot so there's a transition to stratified squamous because of friction - connective tissue, - loose on top cause lots of cells - elastic cartilage at the bottom - gives it flexibility, lets it bounce back if it seals closed or closes

chondrocytes in hyaline cartilage components

- secrete large amounts of ECM - creates a basophilic territorial matrix which is high in proteoglycans - the cells are trapped within this matrix in small spaces called lacunae - these spaces are derived from chondroblasts

Herniated disc

- this is what happened when the annulus gets worn down or torn

how is a herneated disc usually treated?

- usually by opening up the backside of the actual vertebrae - laminectomy

Spongy bone: Osteoblasts

- usually on the edges of the bone tissue - lays down the osteoid initially - derived from osteogenic cells

Osteoarthritis

- very common - characterized by defects in articular/hyaline cartilage within the joint - injury or wear and tear is the cause - cartilage as little regenerative potential - no cure, severely affected joints usually get replaced - difficulty is that the body will try to repair it but can't because the hyaline cartilage in these joints doesn't have perichondrium - tries to repair with fibrocartilage, but it doesn't hold up in a real movable synovial joint and it gradually breaks down

how are osteocytes formed?

- what happens is the osteoblasts finally start to fully differenriate and they pump up the calcium phospate and allow crystals to form so osteoblast is trapped and now it's called in osteocytes - blasts become cytes - single linegage - progentiors which are in the periosteum and become osteoblasts, which trigger osteoid production and they calcify and become trapped and become osteocytes

Inorganic component of the ECM of the bone

- ~65% of the dry weight - consists of hydroxyapatite crystals: calcium and phosphate - this is why the bone has little diffusion cause the crystals prevent easy diffusion - rigid - low diffusion therefore must be highly vascularized - deposited late by osteoblasts and osteocytes in lacunae - crystal form first on collage fibers extracellularly

Annulus fibriosis

-outer ring of fibrocartilage - protects and confines nucleus pulposus - gives disc tensile strength due to high collagen type I fiber content

what is hyaline cartilage composed of?

1) 70% water 2) 20% collage: most often type !! fibers which are intermediate in thickness and strength 3) 10% proteoglycans **these attract water due to high sodium content - Well-defined perichondrium, with limited regenerative potential - Found in joints, nose and trachea (most prevalent type of cartilage)

bone tissue: compact bone

1) Forms the dense outer 'cortex' of the bone organ 2) made up of closely packed cylinders that are formed of concentric layers of bone tissue = 'osteon'

compact bone: osteocyte

1) Osteocyte trapped in bony lamella/layer 2) individual osteocytes send out small cytoplasmic processes through tiny tunnels (=canaliculi) that contact other osteocytes and communicate via gap junctions)

endochondral bone formation

1) a hyaline cartilage model of bone forms first 2) blood vessels invade the cartilage and drag in osteoprogenitor cells with them (called a periosteal bud) 3) increased oxygen tension due to vascularization leads to calcification of the cartilage 4) chondrocyte cell death (ie cartilage death) 5) bone tissue laid down in place of the dead chondrocytes (creating the ossification centre) 6) primary ossification centres form centrally in the shaft of long bones (diaphysis) and secondary ossifications centres form at the ends of long bones (epiphyses) 7) reserve cartilage remained between the diaphysis and epiphysis through puberty (growth plate) 8) growth plate expands until early adulthood to increase the size/length of the long bones, it eventually calcifies and becomes bone

osteoporosis treatment options

1) anti-resorptives 2) anabolics

4 functions of osteoclasts

1) cells adhere to bone very tightly through focal adhesions around the periphery of the cell with actin filaments emanating from them; forms a central sealing zone where bone digestions/resportion will occur 2) cells generate carbonic acid using the cytoplasmic enzyme carbonic anhydrase 3) cells release protons through the transmembrane channels onto the bone surface inside the sealing zone - the acid degrades hydroxyapatite which releases calcium, it is picked up by capillaries to raise serum calcium levels 4) cells release lysosomal enzymes and metalloproteases that digest collagen and osteoid

Cartilage lineage

1) chondroprogenitor 2) chondroblast 3) chondrocyte

Fibrocartilage: matrix

1) contains thick bundles of Type I collagen 2) matrix and orientation of collagen fibers provide FC with high tensile strength 3) chondrocytic component 4) resistant to compression

Osteoblasts

1) cuboidal in shape 2) matrix secreting machinery directed to attached surface of the cell (integrin-dependent) 3) prominent rough ER -synthesis organic matrix

Characteristics of Fibrocartilage

1) distinct from hyaline and elastic cartilage *2) matrix contains Type I Collagen *3) NO PERICHONDRIUM 4) resembles dense regular connective tissue, except FC contains chondrocytes in lacunae AND contains fibroblast 5) little to no ability to regenerate

Where is elastic cartilage found?

1) ear 2) nose 3) larynx = specifically the epiglottis which has elastic cartilage for flexibility 4) other places that are require flexibility or to seal things shut

what does hyaline cartilage form?

1) forms an initial form/model for endochondral bone formation 2) forms the growth plate in growing long bones

bone tissue: spongy bone

1) forms central portion of most bone organs 2) made up of interconnected struts of bone tissue (= 'spicules' or 'trabeculae') 3) interface with bone marrow

'Progenitors'

1) in perichondrium (cartilage) or periosteum (bone) 2) stem-like 3) proliferative 4) lineage restricted

Fibrocartilage: found in?

1) intervertebral disks 2) sites of bone attachment

two types of bone formation

1) intramembranous bone formation 2) endochondral bone formation

structure of compact bone

1) matrix is arranged in concentric layers (called lamellae) arranged around a central canal 2) forms cylindrical columns of bone tissue called osteons with central/vertical Haversian canals and horizontal Volkmann canals

intramembranous bone formation

1) mesenchyme condenses 2) mesenchymal stem cells generate cells of the osteogenic lineage 3) bone forms directly within the mesenchymal condensations 4) important for flat bone formation (bones of the skull, initial formation of the scapula)

Hyaline Cartilage characteristics

1) most abundant type of cartilage 2) found in JOINTS, NOSE, TRACHEA 3) has a transluscent, glassy appearance 4) usually has a perichondrium - lower regenerative capacity than bone 5) entirely Organic ECM 6) very hydrated 7) resists compression 8) facilitates movement between surfaces due to very low friction coeffecient 9) has some tensile strength because of collagen II fibers

Interbertebral disks are made up of what two parts

1) nucleus pulposus 2) annulus fibrosis

components of the ECM of bone

1) organic = osteoid 2) inorganic = mineralized

Bone/osteo lineage

1) osteoprogenitor 2) osteoblast 3) osteocyte

what are the two layers of the periosteum

1) outer fibrous layer 2) inner cambium layer

what drives the osteoprogenitor differentiation?

1) paracrine factors produced by connective tissue fibroblasts 2) endothelial cells 3) pericytes of vasculature (eg. 'Bone Morphogenic Protein', 'Transforming Growth Factor-ß) !

Hyaline Cartilage components

1) perichondrium 2) Cg = chondrogenic progenitor cells derived from mesenchymal cells 3) Cb = chondroblasts derived from chondrogenic progenitor cells 4) C = chondrocytes

'Blasts'

1) some proliferation 2) start to differentiate 3) lay down matrix

similarities of cartilage and bone

1) specialized forms of connective tissue 2) share a mesenchymal origin 3) contain cells embedded in an ECM that they have produced 4) functions of both rely on the composition and structure of their ECMs 5) both can be covered with a thin layer of dense irregular connective tissue (periosteum in bone; perichondrium in cartilage) that is protective and may contain progenitor/stem cells that are normally lineage-restricted

what are the two types of bone tissue within bone organs?

1) spongy bone 2) compact bone

Osteocytes

1) stellate shape 2) located in lacunae (small spaces in matrix); 3) send out processes through very small tunnels in the bone matrix called canaliculi 4) communicate with other osteocyte processes via gap junctions -mature bone cell

Osteoprogenitor cells

1) stem activity (can proliferate and differentiate) 2) lineage-restricted 3) derived from mesenchymal stem cells 4) flattened/elongated.

'Cytes'

1) terminally differentiated 2) trapped in matrix = lacunae

elastic cartilage: characteristics

1) very similar to HC 2) contains elastic fibers 3) elastic fibers impart EC with greater flexibility 4) chondrocytes are more abundant and larger than in HC 5) less matrix than HC 6) well defined perichondrium containing elastic fibers

Types of cartilage

1. Hyaline Cartilage (HC) 2.Fibrocartilage (FC) 3. Elastic Cartilage (EC)

terminally differentiated

A cell sufficiently committed to a particular function that it can no longer divide

Elastic cartilage (EC)

Decreased matrix/increased number of cells compared to hyaline cartilage - Type II collagen + Elastic fibers present in the matrix - Well-defined perichondrium, with limited regenerative potential. - Found in very flexible areas (eg. outer ear) - The EPIGLOTTIS (roof of the larynx) contains a core elastic cartilage that is surrounded by loose connective tissue on which sits a layer of epithelium that transitions from respiratory epithelium (pseudostratified) to stratified columnar to stratified squamous

synovial joints

Example of cartilage and bone articulations between long bones; have a capsule and inner cavity

osteoarthritis and inflammation

Inflammation is not a major cause of osteoarthritis (very different from Rheumatoid Arthritis where chronic inflammation contributes to overall joint degeneration)

Cellular Differentiation

The process where a cell changes from one cell type to another. Most commonly this is a less specialized type becoming a more specialized type

cartilage vs bone: regeneration and repair

after trauma or injury, overall repair and regeneration are much more efficient in bone than in cartilage

all bones start out as

cartilage

anti-resorptives

decrease osteoclast activity acting as non-digestible hydroxyapatite mimics (bisphosphonates/ fosamax)!

osteoclasts are derived from?

hematopoietic stem cells

Perichondrium

is a layer of dense irregular connective tissue that surrounds the cartilage -Fibrous outer layer and inner cellular layer whose cells secrete cartilage matrix. -supply nutrients to cartilage note: when cartilage isn't covered in joints, it gets nutrients from synovial fluid

Osteon

or Haversian System is the fundamental functional unit of much compact bone. Osteons are roughly cylindrical structures that are typically several millimeters long and around 0.2mm in diameter.

basophilic means

substance binds basic dyes like hematoxylin (in this case due to negative charge of GAGs on proteoglycans in ECM) hematoxylin-blue 'basic' dye

xrays and cartilage and bone

xrays can get through cartilage but not through bone