Bone and cartilage

From Iusmhistology

• started here on 02/21/11 at 1PM.

Contents 1 Bone and Cartilage 1.1 Evaluating bone health in the clinical setting 1.2 Bone cells 1.2.1 Osteoclasts 1.3 Osteoblast 1.4 Osteocyte 1.4.1 Genetic profile differs from osteoblasts 1.5 Bone matrix 1.6 Tyeps of bone tissue 1.6.1 Woven bone 1.6.2 Lamellar bone 1.7 Bone anatomy 1.7.1 Haversion systems 1.7.2 Periosteum 1.7.3 Endosteum 1.8 Structures 1.8.1 Lamellae 2 Cartilage 2.1 Hyline cartilage 2.2 Fibrocartilage 2.3 Elastic cartilage

Bone and Cartilage

• Starting a series of three lectures: today, Wednesday (development), and Monday (metabolic regulation).
• Chronic musculoskeletal issues are huge!

Evaluating bone health in the clinical setting

• Most important diagnostic is bone density imaging.
  • DXA = dual energy xray a?
  • We have a huge reference population on which to base our results.
  • Disadvantages:
• High resolution CT scanners
  • Pretty and pretty amazing
  • Becoming more common

• Serum / urine biomarkers:
  • These are markers that can help us know how much osteoblast and osteoclast activity and bone resorption activity.
  • Go back to this list after the lecture.
  • Don't need to know all of these

• Bone biopsy
  • Take a coring tool, core out some from the iliac crest.
  • Then take a histological slide.
  • Not used very much.
  • Used when biomarkers just don't tell you what you need to know.
  • However, histology is very important for clinical trials

Bone cells

Osteoclasts

• Large
• Multiple nuclei
  • More nuclei = more metabolically active
• Much larger than any surrounding cells
• Originate from hematopoietic lineage
  • HSC sits in a macrophage CFU in the bone marrow
  • Become monocites
  • Stay in bone marrow
  • Become osteoclast
  • Rank ligand essential for diff into preosteoclast and full osteoclast.
• Rank ligand
  • Made by osteoblasts
  • Made by other cells of the bone marrow.
  • Attaches to rank receptor on pre-osteoblasts
• Multiple osteoclasts fuse to form multinucleate
• OPG
  • A decoy receptors for rank ligand
  • Can keep osteoclasts from developing by sucking up all the rank ligand
• After maturation and getting to bone surface it starts to resorb bone
• Sealing zone is generated to attach firmly to the bone
  • Allows the osteoclast to target where resorption will occur
  • Compartmentalizes the enzymes
  • Generates a "focal zone"
• Ruffled boarder is generated
  • Increases the amount of surface area so enzymes can be pumped out of the cell onto the bone in high amounts.
• Enzymes for resorption:
  • TRAP
    • Tartrate-resistant alkaline phosphatase
    • Can be assessed in blood to know how much activity of osteoclasts is occurring
  • Cathepsin K
• Houshets lacuna
  • Well in bone where resorption has occurred.

Osteoblast

• Located on bone surface
• Secrete osteoid
  • Osteoid is unmineralized
• Osteoid ges minieralized eventually.
• Come from mesenchymal cells
  • Need runks2 and ostrix
  • Without you get no bone
• Runks2
• Ostrix
• Alkaline phosphatase is key protein involved in matrix production
• Osteoblasts become: osteocytes, bone lining cells, or it can undergo apoptosis.
• Osteoblasts secrete osteoid until their signal to secrete goes away then it beocmes one of thse three fates.
• Bone lining cells:
  • Flattened
  • Lay on bone surface
  • Can still become activated
  • In a nomral state, these cells line the entire bone.
  • Signal can cause them to plump back up and resume bone formation.

Osteocyte

• Most abundant of cells of the bone
• Third cell within bone
• Impt for sensing signals within the bone
• These are terminally differentiated
• Surrounded by osteoid or mineralized matrix.
• MOst abundant of bone cells
• Connected to each other and to the bone surface by filopodial processes
  • These live in channels called canaliculi
  • Connected via gap junctions.
• There is one osteocyte per lacunae.
• Perform matrix maintenance and mechanics.
• This is an intricate network of osteocytes
  • Trading nutrients
  • Sending information

Genetic profile differs from osteoblasts

• Osteocyte cannot produce any more matrix
• Has different functions than the osteoblast
• Don't memorize the table
• Sclerostin is a gene unique to osteocytes and not osteoblasts.
  • This shows up in late an osteocytes differentiation.
  • It inhibits bone formation
  • We are trying to develop drugs to inhibit sclerostin help grow bone.

Bone matrix

• Made of type 1 collagen.
  • A fibrous collagen.
• Takes on a staggered arrangement.
  • Mineral connects them end to end.
• The fibrils are highly crosslinked
  • Promotes structural rigidity.
• Mineral interspersed also adds rigidity.
• Fragments of crosslinks can be used to measure bone turn over.
• C-propeptide in the blood means there is bone formation

When does collagen get cleaved?

• Collagen is formed in a twisted plywood formation.
  • This gives strength to the bone.
  • So its like people and they it is twisted in an orientation that will maximixe the structural integrity.

• Non-collagenous components:
  • Know osteopontin, osteonectin, and ostecalcin
  • Osteocalcin is a biomarker that can be measured in the blood to know how much osteoblast activity (bone formation) there is.

• Bone mineral
  • Mineral goes between adjacent collagen fibers and in the space between.
  • As it accumulates it first goes between length wise.

Tyeps of bone tissue

Woven bone

• AKA primary bone and Immature bone
• Not very common in the adult skeleton
• Found only when there is a bone injury or in some pathological state
• This is the type of bone that is formed when you need bone right now.
  • Provides rapid stabiliation
• Not very organized
• Osteoid spit out in all directions
• Relatively low mechanical strength.

Lamellar bone

• AKA secondary bone, mature bone
• Most of the bone oin our bodies is this type
• Highly organized
  • As mentioned above
• Formed slowly
• Higher mecanical strength than primary.
• Lamellae:
  • Differing patterns of collagen organization
  • Result in high birefringence
    • The ability to refract light differently.
  • This is a product of the alternating pattern of collagen fibers.

Bone anatomy

• Cortical or cancellous bone
  • Cortical is called compact
    • This is the outer part
    • Main fxn is structural
    • PRovide resistance to loading
  • Cancellous bone = spongy bone = trabecular
    • NOT squishy
    • Small piece of cancellous and small piece of cortical would looke the same.
• Four different surfaces:
  • Outer surface is called the periosteal surface
  • Within are the cancellous surfaces
  • Endocortical surface is the inside of the cortical surface.
  • Within cortical bone are the haversion units.
  • KNow the four surfaces

Haversion systems

• AKA osteons
• An osteon is a unit of bone that the osteoclasts have dug out and then replaced within the cortical unit of the bone.
• Within the haversion system is a space where the blood vessels and nerves flow.
• The center part of this haversiona canal is the central canal.
  • Run along the long axis of the bone
• Perferating canals = volkman (?) canals
  • Go perpendicular to the long axis of the bone
  • House vessels and nerves
• OUter edge of osteon is called the cement line.

Periosteum

• This layer is tightly adherent to the bone
• Both cellular and fibrous layers

Endosteum

• Endosteum is similar to periosteum but is on the inside of the bone
  • Endostium has only cells.

Structures

Lamellae

• Concentric lamellae:
  • These are concentric.
  • Each ring from the outside of the bone in are called lamellae.
  • Associated with a central canal.
• External circumferential lamellae**WRap all the way around the bone.
• Interstitail lamellae
  • Within the bone tissue but not associated with central canals

Cartilage

• Cells are housed in lacunae which are surrounded by matrix.

Hyline cartilage

• Found in joints, respiratory passages, ends of ribs, within bones
• Made of type 2 collagen fibrils
• Has some non-collageneous proteins proteoglycan aggregates.
• Proteoglycan aggregates
  • Have a central core
  • Have some protein cores and then glycoaminoglycans hanging off.
• PG attract water and can therefore act as a shock absorber.

• Chondronectin
  • Holds cells in place on the collagen and proteoglycans

• Condrocytes:
  • Retain mitotic activity
    • Unlike osteoclasts
  • Can form 2, 4 or even more cells within its region.
  • These units are called isogenous groups.

• Hyline matrix:
  • It is not uniform.
  • Terirtorial matrix = capsular
    • Found just around a chondrocyte
    • Capsule is found closer
  • INterteritorial matrix
    • Found farther out.
  • The collagen fibrils are smaller in the territorial matrix
  • The types of pg are different in the territorial than interterritorial.

• Perichondrium
  • Fibrous tissue that lines the outside of hyline cartilage in most but not all locations of hyline cartilage
  • Allows connection of muscle to cartilage
  • Supplies the cells that can differentiate into chondroblasts (which diff into chondrocytes)

Fibrocartilage

• Found mostly in IV disks
• Has type 1 collagen in it.
  • Forms fibers called rows or chords
• Between chords are the chondrocytes
• Has no perichondrium
• Can serve as a transition between tissues like tendon and bone.

Elastic cartilage

• Found in the ear, epiglottis, and the larynx
• Has type 2 collagen
  • Fibrils
• Elastic fibers also present
• Has a pericondrium
• Looks much like hyline but you can see fibers in it.

• stopped here on 02/21/11 at 3PM