Bone Tissue

Question 1

Bone tissue

Answer 1

Bone tissue

• Functions:
  
  • provide solid support for the body
  • protects vital organs
  • encloses internal cavities containing bone marrow
  • reservoir of Ca2+, phosphate and other ions
  • system of levers
• Specialized CT composed of bone matrix

Question 2

Endosteum & Periosteum

Answer 2

Endosteum- lines the internal surface surrounding the marrow cavity

• covers small trabeculae of bony matrix that project into marrow cavities
• also contains: osteoprogenitor cells, osteoblasts (for bone growth), & bone lining cells
• sparse delicate matrix of collagen fibers

Periosteum- lines the external surface

• outer fibrous layer of dense connective tissue
• type 1 collagen, fibroblast, blood vessels
• Perforating or Sharpey’s fibers- periosteal collagen that penetrate the bone matrix and bind the periosteum to the bone
• Inner layer (more cellular): osteoblasts, bone lining cells, osteoprogenitor cells (mesenchymal for growth & repair)

Question 3

3 major cell types of bone tissue

Answer 3

3 major cell types of bone tissue:

1. Osteocytes
   * found in lacunae between lamellae with cytoplasmic processes in canaliculi
2. Osteblast

• growing cells
• secrete osteoids (mineralized vesicles)

3. Osteoclasts

• giant mulitnucleated cells
• involved in removing calcified bone matrix & remodeling bone tissue

Question 4

Osteoblasts

Answer 4

Osteoblasts

• originates from mesenchymal stem cells
• produce organic compounds of bone matrix including Type 1 collagen fibers, proteoglycans, matricellular glycoproteins (osteonectin)
• active osteoblasts
  
  • located exclusively at surface of bone matrix
  • bound by integrins
  • joined by adherent & gap junctions
• differentiate as osteocytes
• Prominent among the noncollagen proteins secreted by osteoblast is osteocalcin (Vit K-dependent)
  
  • binds Ca2+ & concentrate mineral locally
  • release membrane-enclosed matrix vesicles rich in ALP
  • raise PO43
  • Hydroxyapatite [Ca₁₀(PO₄)₆(OH)₂]- 1st step in calcification
• Osteosarcoma- bone cancer arising in osteoprogenitor cells
• Skeleton is often site of secondary metastatic tumors (cancer via small blood or lymph vessels from breast, lung, prostate, thyroid)

Question 5

Osteocytes

Answer 5

Osteocytes

• communicate with one another & ultimately with nearby osteoblasts & bone lining cells via gap junctions at the end of their processes
• normally the most abundant
• almond-shaped
• exhibit less RER, smaller Golgi, & more condensed nuclear chromatin
• maintain calcified matrix
• death is followed by rapid matrix resorption
• lacunar-canalicular network serve as sensitive detectors of stress or fatigue-induced microdamage in bone
• Mechanostat
  
  • network of dendritic processes that signal cells to adjust ion levels & maintain adjacent bone matrix
  • lack of exercise (or weightlessness by astronauts) decrease bone density d/t lack of mechanical stimulation of osteocytes

Question 6

Osteoclasts

Answer 6

Osteoclasts

• large, motile cells with multiple nuclei (d/t origin from fusion of bone marrow derived monocytes)
• essential for matrix resoprtion during bone growth & remodeling
• development requires 2 polypeptides produced by osteoblasts:
  
  • macrophage-colony stimulating factor (M-CSF)
  • receptor activator of nuclear factor-kB ligand (RANKL)
• lie in matirx known as resorption lacunae (Howhsip lacunae)
• Active osteoclast:
  
  • sealing zone (bind cells to bone matrix)
  • ruffled border (surface projections)
  • pump proton (H⁺) to acidify & dissolve hydroxyapatite
  • release matrix metalloproteinases & other hydrolytic enzymes for localized digestion of matrix proteins
• Osteopetrosis
  
  • heavy bones (marble bones)- obliterates marrow activities- leading to anemia
  • osteoclasts lack ruffle borders & bone resorption is defective
  • mutations in gene for cells’ proton ATPase pumps on Cl channels
• Osteoporosis
  
  • bone resorption exceeds bone formation
  • found in immobilized patients & post-menopausal women
  • Ca²⁺ loss from bones reduced bone mineral density (BMD)
  • Dual-energy X-ray Absorptiometry- routine scan for BMD

Question 7

Bone matrix

Answer 7

Bone matrix

• ​inorganic (no carbon)
  
  • Calcium hydroxyapatite [Ca10(PO4)6(OH)2] is most abundant
  • bicarbonate, citrate, Mg²⁺, K⁺, Na⁺ are also found
• organic (with carbon)
  
  • 90% Type 1 collagen, small proteglycans, multiadhesive glycoproteins (osteonectin)
  • Osteocalcin & Phosphatases promote calcification
• decalcified bone matrix is acidophilic d/t increase collagen content

Question 8

Types of Bone

Answer 8

Types of Bone:

1. Compact (cortical bone)

• 80% of all lamellar bone
• parallel lamellae or densely packed osteons with interstitial lamellae
• located at thick, outer region (beneath periosteum) of bones

2. Cancellous (spongy bone, trabecular bone, medullary bone)

• 20% of all lamellar bone
• interconnected thin spicules or trabeculae covered by endostem
• found in inner region of bones, adjacent to marrow cavities

Question 9

Short bones and Flat bones

Answer 9

Short bones

• wrist & ankle
• cores of cancellous bone
• surrounded by compact bone

Flat bones

• calvaria (skull cap)
• Plates- 2 layers of compact bone
• Diploe- separates plates with cancellous bone

Question 10

2 types of bone organization

Answer 10

2 types of bone organization:

1. Lamellar bone/Mature/Secondary bone

• characterized by multiple layers of lamellae of calcified matrix
• Heavily calcified
• Not all lamellar bones have osteons
• All normal regions of adult bones
• Type 1 collagen fibers are aligned in each lamellae
  
  • oriented orthogonally in successive lamellae
  • orientation adds strength of lamellar bone
• Osteon (Haversian system)
  
  • complex of concentric lamellae (5-20)
  • surrounds central canal (contains blood vessels, nerves, & endosteum
• Lacunae
  
  • found between successive lamellae
  • each one with one osteocyte all interconnected by the canaliculi containing the cells’ dendritic processes.
  • processes are in contact with gap junctions
• Cement line- outer boundary of each osteon
• Perforating canals (Volkmann canals)- transvers canals to communicate different canals
• Interstitial lamellae
  
  • scattered among the intact osteons
  • lamellae remaining from osteons destroyed by osteoclasts
• External circumferential lamellae- beneath the periosteum
• Internal circumferential lamellae- around the marrow cavity which encloses & strengthens the middle region containing osteons

2. Woven bone/Immature/Primary bone

• nonlamellar
• random distribution of Type 1 collagen fibers
• 1st bone to appear in embryonic development & fracture repair
• temporary & replaced in adults by lamellar bone except in sutures of calvaria & insertions of tendons
• lower mineral content
• higher proportion of osteocytes

Question 11

Bone remodeling

Answer 11

Bone remodeling

• occurs througout life
• resorbs part of old osteons & produce new ones in compact bone
• process:
  
  • osteoclasts remove old bone
  • small tunnel-like cavities are formed
  • tunnels are quickly invaded by osteoprogenitor cells
  • osteoblasts develop, line wall of tunnels, secrete osteoid
  • forms new osteon (concentric lamellae and trapped osteocytes)
• 5-10% of the bone turns over annually (200X faster in active young children)

Question 12

Osteomalacia & Osteitis fibrosa cystica

Answer 12

Diagnosis on the conditions below can be aided with antibiotic tetracycline in which fluorescent lamellae can be seen on bone formed

Osteomalacia - condition in which bone mineralization is impaired

Osteitis fibrosa cystica- increased osteoclast activity resulting in removal of bone matrix & fibrous degeneration

Question 13

2 process of Osteogenesis

Answer 13

2 process of Osteogenesis

1. Intramembranous ossification (fetus before 8 weeks)

• Osteoblast differentiate directly from mesenchyme & begin secreting osteoid
• which most flat bones (skull, jaws, scapula, clavicle) begin to form
• Ossification centers:
  
  • Osteoprogenitor cells arise
  • proliferare
  • form incomplete layers of osteoblasts around a network of developing capillaries
  • Osteoid secreted calcifies forming woven bone with osteocytes in lacunae & cannaliculi
  • continued matrix secretion & calcification enlarges areas
  • fusion of neighboring ossification centers
  • woven bone is replaced by compact bone (encloses cancellous bone)
  • Mesenchymal regions that do not undergo ossifcation give rise to endosteum & periosteum

2. Endochondral ossification (8 weeks or 2 months)

• preexisting matrix of hyaline cartilage is eroded & invaded by osteoblasts (begins osteoid production)
• forms most bones of the body
• Appositional growth
• Primary ossification center forms in diaphysis (1st trimester):
  
  • begins with hyaline cartilage as a mold
  • Bone collar produced by osteoblasts differentiate within the perichondrium (transitioning to periosteum) around the cartilage model’s diaphysis
  • the collar impedes diffusion of O2 & nutrients causing local chondrocytes to swell up (hypertrophy) releasing osteocalcin & ALP
  • the hypertrophic chondrocytes eventually die creating empty spaces within the calcified matrix
  • Blood vessel from the perichondrium (now periosteum) penetrate the bone collar bringing osteoprogenitor cells to the porous central region
  • Osteoblasts move into available spaces & produce woven bone
• Secondary ossification centers form in epiphyses (birth):
  
  • Bone replaces cartilage except the articular cartilage & epiphyseal plates
  • Epiphyseal plate separates Primary & Secondary ossification centers for continued bone elongation (until 20 yrs old)
  • Epiphyseal plates ossify & form epiphyseal lines (epihyseal closure
  • Articular cartilage remain

Question 14

Osteogenesis imperfecta

Answer 14

Osteogenesis imperfecta

• brittle bone disease
• osteoblasts produce deficient amounts of Tyoe 1 collagen or defective Type 1 collagen mutation
• fragility of bones

Question 15

Distinct zones of Epiphyseal growth plate

Answer 15

Distinct zones of Epiphyseal growth plate:

1. Zone of Reserve (or Resting)
   * composed of hyaline cartilage
2. Zone of Proliferation

• cartilage cells divide repeatedly
• cells enlarge & secrete more Type II collagen & proteoglycan
• cells are organized into columns

3. Zone of Hypertrophy

• swollen chondrocytes
• compressed matrix into aligned spicules
• stiffens matrix by secretion of type X collagen which limits diffusion in the matrix and with growth factors promotes vascularization from the adjacent primary ossification center

4. Zone of Calcified Cartilage

• chondrocytes about to undergo apoptosis release matrix vesicles & osteocalcin to begin matrix calcification by the formation of hydroxyapatite crystals
• chondrocytes have disappeared, hence the white blank color

5. Zone of Ossification

• bone tissue appears first
• capillaries & osteoprogenitor cells invade
• Osteoblasts secrete osteoid which becomes woven bone & remoldeled to lamellar bone

Question 16

Rickets

Answer 16

Rickets (No D :(

• Ca²⁺ deficiency in children
• failure to produce vitamin D which is important for absorption of Ca2+
• Bone matrix does not calcify normally that makes epiphyseal plate become distorted & bone grows slowly & often deformed

Question 17

Parathyroid hormone (PTH) & Calcitonin in bone formation & resorption

Answer 17

Parathyroid hormone (PTH)

• from parathyroid glands
• Indirectly raises blood calcium levels by stimulating osteoblast to release OSF (osteoclast-releasing hormone) which can stimulate the osteoclast to resorb matrix by binding to its receptor

Calcitonin

• secreted in the parafollicular cells (C cells) that are neuroendocrine cells in the thyroid gland
• Directly reduce elevated blood Ca²⁺ by binding to osteoclast inhibiting its function and at the same time promotes bone formation by the osteoblasts

Question 18

Bone Repair

Answer 18

Bone Repair

• (with periosteum in place) Clotted blood is removed by macrophages
• a fibrocartilaginous (soft) callus forms
• invaded by regenerating blood vessels & proliferating osteoblasts
• fibrocartilage is replaced with a hard (bony) callus
• Bone is remodeled

Question 19

Joints

Answer 19

Joints

• regions where adjacent bones are capped and held together firmly by other connective tissue
• Synarthroses- very limited or no movement
  
  • Synostoses
    
    • bones link to other bone
    • unite skull bone (sutures in children)
  • Syndesmoses
    
    • join bones by dense CT only
    • example: interosseus ligament of the inferior tibiofibular joint & the posterior region of sacroiliac joints
  • Symphyses
    
    • thick pad of fibrocartilage between the thin articular cartilage convering the ends of the bones
    • example: intravertebral disc & pubic symphysis
• Diarthroses
  
  • permit free bone movement
  • elbow & knee
  • allow great mobility
  • ligament & capsule of dense CT maintain proper alignment of bones
  • joint cavity, synovial fluid, synovial membrane
  • 2 specialized cells:
    
    • Macrophage-like synovial cells (type A cells)
      
      • derived from monocytes
      • remove wear & tear from synovial fluid
    • Fibroblastic synovial cells (type B cells)
      
      • produce abundant hyaluronan & sparse proteoglycan transported by water
  • Articular surface is made of hyaline cartilage (lacks perichondrium)

Question 20

Pituitary dwarfism, Gigantism, Acromegaly, RA

Answer 20

Pituitary dwarfism- lack of growth hormone

Gigantism- excess of growht hormone

Acromegaly- increase in growth hormone in adults (increase in width by periosteal growth which thickens long bones)

RA (Rheumatoid arthritis) - chronic inflammation of synovial membranes