Bone Flashcards by Raeann Whitney

Cell types found in bone

Osteoblasts, osteocytes, osteoclasts

Blood and defense cells

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Components of bone matrix

Fibers (collagen type I, proteoglycans)

Mineral (Calcium phosphate crystals)

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Organic component of bone matrix (collagen I and proteoglycans)

Osteoid

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The end of a long bone

Epiphysis

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The shaft of long bone

Diaphysis

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A tough, dense connective tissue model, gives the bone residency and defines the organization of the CaPi crystals
Primarily Type I collagen

Osteoid

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Gives the bone its strong resistance to compression and bending
Very brittle without osteoid

CaPi crystals (mineral component)

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Dense bone tissue predominates, permeated by small vascular channels

Compact bone

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Thin spicules or trabeculae, with larger vascular channels, marrow space

Cancellous = spongy = trabecular bone

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End of a long bone; compromises cancellous bone with shell of compact bone (and articular cartilage and epiphysial plate)

Epiphysis

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Shaft of long bone; compromises marrow cavity surrounded by cylinder of compact bone

Diaphysis

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Covers the bone surface facing the marrow. It is the layer, more or less continuous, of bone lining cells (resting) and osteoblasts (active) that covers the bone surface facing the marrow cavity.

Endosteum

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Covers the outer surface of the bone. It compromises a) an inner layer of bone lining / osteoblasts equivalent to (and continuous with) the endosteum; and b) an outer layer of dense CT, blood vessels and nerves. (where you can sense pain)

Periosteum

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Two pathways for embryonic bone formation

Intramembranous bone formation

Endochondral bone formation

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Pathway for embryonic development of flat bones (membrane bones) of skull. Islands of osteoid are deposited in loose CT,, grow, and coalesce.

Intramembranous bone formation

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Pathway for embryonic development of most bones, in particular long bones. Bone deposition is preceded by cartilage model. Complex process.

Endochondrial bone formation

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All bone growth is ____________ - osteoblasts deposit bone on existing layers of osteoid

appositional

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__________ make bone

Osteoblasts

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__________ maintain bone

Osteocytes

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__________ destroy bone

Osteoclasts

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During initiation of intramembraneous bone formation, ______________ cells differentiate to osteoblasts, line up side by side and secrete osteoid.

Mesenchymal cells

Mesenchyme (undeveloped loose CT)

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The ____________ does two things:

a. Secretes osteoid (the collagen type I defines orientation of bone tissue (CaPi crystals will align parallel to fibrils)
b. Initiates mineralization - by secreting alkaline phosphatase

osteoblast

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How is mineralization initiated in bones and teeth, but blocked in ectopic locations?

Pi + Ca are near the precipitation point (very concentrated) in all tissues.
Pyrophosphate (PPi) is present in tissue fluids, and is actively secreted by some cells (smooth muscle in artery). PPi blocks precipitation of CaPi (mineralization).
Osteoblasts secrete alkaline phosphatase, an enzyme that cleaves PPi and removes the inhibition. (No PPi, CaPi precipitates.)

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_____________ blocks mineralization of bone by preventing the precipitation of CaPi.

Pyrophosphate

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________________ cleaves pyrophosphate and allows for mineralization

Alkaline phosphatase

Two things necessary and sufficient for mineralization of a tissue

1. A matrix of collagen fibrils, which serve as the scaffold for CaPi crystals. Normally this is collagen type I, but type II (cartilage) can also be mineralized. 2. Alkaline phosphatase, which cleaves pyrophosphate and removes the inhibition of crystallization.

Transfer of nutrients begins with the _____________ on the inner layer (endosteum), which are in contact with extracellular fluids. They send out thin processes into the bone that contact similar processes from the first layer of osteocytes. The first layer of osteocytes sends processes deeper into the bone that connect with processes from the second layer.

Bone lining cells

Processes connect via ___________

gap junctions

______________ are derived from osteoblasts as the cells are trapped in bone matrix.

Osteocytes

____________ live in lacunae, with long thin processes in canaliculi.

Osteoclasts

Osteocytes can live no more than 100 microns from a blood space. This defines the radius of _________.

Osteons

Little tunnels that contain osteocyte processes

Canaliculi

What are speculated functions of osteocytes?

Remove and re-deposit Ca in their vicinity, in response to PTH? Mechano-sensors (microfractures would cut off osteocyte processes which might lead to a signaling response to direct repair?)

Islands of bone have grown together, entrapping blood vessels. Woven bone. Produced by original embryonic process. Blood canals run in random directions, collagen is nor organized.

Primary Haversian system

The blood vessel and surrounding bone

Haversian system

(lamellar bone) Cylindrical lamellae of bone, parallel to axis of compression; produced by remodeling Optimized for compression

Secondary Haversian system

1. Large multinucleate cells, related to monocytes/macrophages (not related to osteocytes) 2. Digest bone a. Secretes acid, dissolves CaPi b. Secretes acid hydrolyses, digest osteoid

Osteoclasts

An __________ forms a sealed contact with bone surface to ensure very controlled erosion of bone. Ruffled border secretes acid and protein hydrolyses.

osteoclast

How is bone remodeled?

Osteoclasts form resorption cavity Osteoblasts come in to make new bone Osteocytes Haversian canal

Cell that: 1. Detects defective bone - dead bone (no osteocytes) or microfractures 2. Detects the direction of compressive load. Drills tunnel in that direction. 3. Knows that the osteocyte network can only function 100 microns from the blood vessel,, so it stops when the tunnel is 200 microns in diameter.

Osteoclast

______ fibrils that make up the osteoid are carefully arranged in opposite directions for each lamellae

Collagen

______________ interconnect Haversian canals and osteons

Volkmann's canals

The basic structural unit of compact bone | (Haversian system(

Osteon

Features of the osteon (Haversian system)

1. cylinder, axis in direction of compressive load 2. ~200 microns (.2mm) outside dimeter 3. 3-5 concentric lamellae of bone matrix; osteocytes between lamellae 4. Haversian canal at center (~20 microns diameter) contains blood vessel

1. Replaces dead bone tissue. 2. Orients osteons in the direction of recent load. 3. Maintain bone mass to support load, but minimize excess. Bone mass is constantly being fine-tuned. 4. Provides a storage bank for calcium. Removal and deposition of calcium is balanced to maintain calcium in blood. 500 mg calcium remodeled each day.

Bone remodeling

"Lake" in which osteocytes sits in bone matrix

Lacuna

Excess unfilled resorption canals, and depletion of cancellous bone. Loss of bone to the danger point of fracture from normal activities.

Osteoporosis

The _____________ is 30% for a young adult: bone mass is 30% more than needed to prevent fracture from normal stress.

Safety factor

Bone resorption is stimulated by:

1. Reduced load (astronauts, bedridden patients) 2. PTH (regulates body calcium) Elevated PTH at a constant level causes removal of Ca from bone 3. PTH-RP (PTH related hormone). Normally expressed durning embryonic development, but re-expresed in some tumors. **These involve activation of osteoclasts and/or inhibition of osteoblasts

Structural features of osteoporosis

An excess of unfilled resorption canals Thinning of cortical bone, excess erosion at the endosteal surface (marrow) - reduced thickness of compact bone Erosion of cancellous bone - this is at least as important as cortical bone for overall bone strength

Causes of bone loss

Excess respiration by osteoclasts or insufficient deposition of new bone by osteoblasts (or both)

Therapies for osteoporosis (inhibit bone loss):

Bisphosphonates inhibit osteoclasts | rPTH (recombinant PTH) in a pulsatile fashion to stimulate osteoblasts and generate new bone

_______________ bone formation steps: 1. Formation of the cartilage model 2. Bony collar 3. Chondrocyte hypertrophy; matrix compression and calcification 4. Invasion of vascular bud a. macrophages clean up dead cells b. osteoblasts deposit bone on calcified cartilage scaffold c. osteoclasts - remodeling 5. Interstitial growth of cartilage at epiphysis makes bone grow longer

Endochondrial

The cartilage bar during endochonrial bone formation points in the direction of the:

long bone

Periosteum calcifies at the _______________. This limits diffusion, triggers chondrocyte hypertrophy, and subsequent events.

bony collar

___________ approaches the bony collar (with macrophages, mesenchymal cells). It erodes the bony color and invades calcified cartilage.

Vascular bud (blood vessel)

__________ growth at the zone of chondrocyte proliferation is confined to the longitudinal direction and makes bones grow longer.

Interstitial

All growth of long bones from birth to adulthood takes place at the ___________, which then disappears near adulthood

epiphyseal plate

__________ of bone bridge and attach the cartilage of the epiphyseal plate to the cortical bone from the shaft

Trabeculae

During a bone fracture, Haversian canals break and bone dies. Bleeding, clot, and acute inflammatory reaction occur. ____________ forms, extending back to living bone and bridging the fracture. Endochondral bone formation occurs within the callus. Bone replaces cartilage and is extensively remodeled.

Cartilage callus

A receptor on pre-osteoclasts that stimulates osteoclast differentiation and activity

RANK

A TGF beta like protein that activates RANK and stimulates osteoclasts

RANKL (RANK ligand)

A soluble decoy receptor for RANKL. It binds RANKL and prevents its binding to RANK. Excess OPG blocks osteoclast activity.

OPG (osteoprotegrin)

Receptor on pre-osteoclasts that induces maturation to osteoclasts

RANK

cytokine that binds and activates RANK

RANKL

How do osteoblasts turn on osteoclasts?

Osteoclast precursor cells have RANK, a receptor | Osteoblasts secrete RANK ligand, activate formation of mature osteoclasts

_________ is a soluble decoy receptor that binds RANKL and inactivates its

OPG (osteoprotegrin)

Osteoblasts have two ways to regulate osteoclasts. They secrete more _________ to activate osteoclasts and secrete more _________ to block activation.

RANL to activate | OPG to block activation

Denosumab, mAb against RANKL can be a treatment for ____________

Osteoporosis

________ is not just secreted by osteoblasts. It is also highly expressed in lymph nodes and thymus, mammary gland, and lung. (No removal of bone, so cavity gets packed with bone.)

RANKL

________ is not just secreted by osteoblasts. 65% in bone marrow is made by B cells. B-cell deficient mice are osteoporotic. (B cell secretion prevents degradation.)

OPG

Regulates calcium and phosphorus levels in the blood by promoting their absorption from food in the intestine, and by promoting re-absorption of calcium in the kidneys Promotes bone formation and mineralization and is essential in the development of an intact and strong skeleton Inhibits PTH secretion from parathyroid gland

Vitamin D

General term for softening of the bones due to defective bone mineralization

Osteomalacia

Osteomalacia in children is known as:

Rickets

A common cause of osteomalacia is a deficiency in:

Vitamin D

In ________, vitamin D3 is produced in S. basale and S. spinosum (layers of stratified epithelium) by UVB irradiation

skin

In _________, vitamin D3 is consistitutively converted to 25(OH)D..

liver

In _________, 25(OH)D is covered to 1,25(OH)2D, the active form, and is related back into circulation. This reaction is highly regulated primarily by PTH, but also by FGF23 (involved in Pi regulation) and IGF-1 (involved in growth).

kidney

Pre-D3 is formed through a photon in UV light, then D3 is formed by ___________. Then 25-OH is added in the liver, and 1-OH is added in the kidney.

Isomerization

How does vitamin D regulate transcription?

1. Vitamin D binds VDR is the cytoplasm. 2. VDR is transported to the nucleus. 3. It forms heterodimer with Retinoid X receptor 4. The VDR-RXR dimer binds vitamin D responsive elements (VDREs) in promoter on DNA and turns on the associated gene

The main function of 1,25(OH)2D is to:

maintain a calcium-phosphorous product in the circulation that is supersaturated, ready for spontaneous calcification of osteoid.

Vitamin D response genes (upregulated by vitamin in) in:

Intestine - ECaC, calbindin: enhances transport of Ca across intestine Osteoclasts - RANKL: bind to RANK receptor on pre-osteoclasts, induces mature osteoclasts Osteoblasts - osteocalcin: enhances insulin secretion and reception, improves glucose handling