Bones Flashcards
What are the roles of bones? (5)
- Support body mass (weight bearing)
- facilitate movement (articulating joints)
- protect vital organs (CNS, thorax)
- site of hematopoiesis (bone marrow)
- calcium reservoir (& other minerals)
What are the similarities between cartilage and bone? (3)
- hard tissues
- contain living cells embedded in the matrix (lacunae)
- common mesenchymal progenitor cells
What are the differences between cartilage and bone? (3)
- bone heavily vascularized/ cartilage avascular
- bone access to blood vessels via canaliculi
- cartilage less calcified, uses long - range diffusion
What type of mechanical stress affects bone structure?
- compression and movement required for proper bone remodeling
- plasticity used by orthodontists to modify position of teeth in jaw
- loss of bone mass during space flight or immobilization
- Piezoelectric potential (-ve, bone deposition: +ve, bone reabsorption)
Both periosteum and endosteum contain osteogenic cells:
- cells that can divide (mesenchymal)
2. cells that can give rise to either osteoblast or chondroblast in function of environment and vascularization
Trabeculae (spicules)
network
Bone Matrix: Non cellular; Organic Components
~ 25 % of total bone mass, mostly fibrous
• Fibers: Collagen type I (90%): provide elasticity, tensile strength
• Ground substance: (amorphous)
- Glycosaminoglycans (chondroitin & keratan sulfates)
- Glycoproteins
- Osteonectin and Osteopontin: anchors minerals to collagen, initiate mineralization and promote crystal formation.
- Osteocalcin and Bone Sialoprotein: calcium binding proteins
• Osteoid: newly secreted organic matrix (not-yet fully calcified)
Bone Matrix: Inorganic Components
- 50-70% of total bone mass
- Provide compressive strength to bones
- Mostly salts of calcium phosphate in amorphous or crystalline form
- Crystals: Hydroxyapatite: Ca10(PO4)6(OH)2
- Contain also calcium citrate, bicarbonate, fluoride
- Water represents ~ 15 % of bone mass.
- Hydration shell around hydroxyapatite crystals facilitate calcium exchange with fluids
Methods to prepare bone sections (2)
- Decalcification - flexible tissue (osteocytes in lacunae)
2. Grinding - translucent ground sections (lacunae with canaliculi)
Bone Cells Related to Bone Formation: (3)
- Mesenchymal osteoprogenitor: osteogenic cell
- Osteoblast: bone forming cells
- Osteocyte: terminally differentiated cells
Mesenchymal osteoprogenitor:
• Osteogenic cell (stem cells)
• Committed mesenchymal cell
• Commitment is controlled by Bone Morphogenic Proteins (BMPs), osteogenin
• Located in inner (mesenchyme/
marrow areas close to bone) and outer linings of bone
• Can self-renew or differentiate:
• Self-renewal controlled by PDGF, TGF, IGF
• Differentiation controlled by BMP, VitD3
Osteoblast:
• Bone forming cell
• Non-dividing cell
• Located on bone matrix surface
• Secrete bone matrix (osteoid, arrow)
• High secretory activity shown by abundant RER, Golgi
• Secretion activated by GH (somatotropin), sex steroids
• Deposition of osteoid (arrow) between osteoblast cell layer and existing bone
Osteoblasts secrete factors that promote osteoclast activity
Osteocyte:
• Terminally differentiated cell
• Osteoblast that became trapped in its mineralized matrix
• Located in spaces called lacunae
• Extend filopodia in canaliculi: canals connecting cells (gap junctions)
• Osteocytic osteolysis
- limited calcium release inside lacunae
- Parathyroid hormone (PTH) increase resorption (chief cells of Parathyroid gland)
- Calcitonin decrease resorption
- (parafollicular cells of Thyroid gland)
Osteoclast:
• Bone resorbing cell
• Macrophage/monocyte lineage
- Multinucleated: fusion of monocytes promoted by Vitamin D
• Large, non-dividing, mobile
• Located on bone resorptive and free surfaces in small cavitations called Howship’s lacunae
• Ruffled border: bone resorption zone inside the Howship’s lacunae
- surrounded by a ring shaped sealing zone: clear zone
- cytoplasmic processes
Osteoclast function
Osteoclastic osteolysis = bone resorption
• Focal decalcification by acidification
(citric acid release, carbonic anhydrase)
• Extracellular digestion by hydrolytic
enzymes (collagenase, acid phosphatase,
sulfatase) for proteolysis
• Required for bone remodeling & repair (disease: osteopetrosis)
• Regulated by:
- PTH (indirect via factors from osteoblasts): increase resorption
- Calcitonin, estrogens: decreased resorption
- Critical role in calcium homeostasis
Periosteum: outer surfaces
• Tough connective tissue membrane
• Covers bone outer surface
(except articular & tendon insertion surfaces)
• Fibrous periosteum (FP):
Outer fibrous layer, highly vascularized
• Osteogenic periosteum (OP):
Inner cellular layer (osteogenic cells,osteoblasts)
• Attached to bone by collagen fiber bundles: Sharpey’s fibers
• Point of origin of Volkmann’s
canals containing blood vessels
Endosteum: inner surfaces
• Thin single cell layer
(progenitor cells, osteoblasts and osteoclasts)
• Lines bone internal surfaces (trabeculae, haversian canals)
• Important for bone nutrition and maintenance
Role of periosteum and endosteum in bone growth, repair and remodeling
- Both contain osteogenic cells:
• Cells that divide (mesenchymal)
• Cells that can give rise to either - osteoblast or chondroblast in function of environment and vascularization
Mesenchymal uncommitted precursor: Vascular
- osteoprogenitor
- osteoblast
- osteocyte
(Intramembranous endochondral)
Mesenchymal uncommitted precursor: Avascular
- Chondroprogenitor
- chondroblast
- chondrocyte
(Appositional Interstitial)
Bone Proper; organization of collagen fibers in matrix determine the types of bone:
• WOVEN: Primary/immature bone
• Random disposition of collagen fibrils, amorphous calcium phosphate
• In embryonic development and during bone repair
• LAMELLAR: Secondary/mature bone
• Organized disposition of collagen fibers (lamellae), crystalline calcium phosphate
- Cancellous (spongy)
- Compact (cortical)
• Comes from remodeling of woven bone
• Adult bone
Mature (Lamellar) Bone: Cancellous (spongy) bone
• Network of irregular lamellae: Trabeculae (spicules) • Large spaces filled with bone marrow: hematopoietic tissue • Mostly converted to compact bone • Exceptions: flat bones (skull diploë) Alveolar bone around teeth Short bones Epiphyses & Diaphysis of long bones • Anastomose: fusion of trabeculae trapping blood and lymphatic vessels inside canals
Mature (Lamellar) Bone: Compact (cortical) bone
• Forms diaphysis of long bones
Found as thin layer around epiphyses
Forms the “tables” of skull’s flat bone
• Highly organized bone lamellae:
- Circumferential (outer and inner)
- Harversian systems (osteons)
- Interstitial (areas between osteons)
• Haversian system: Cylindrical
columns of 4-15 concentric lamellae
surrounding a canal called haversian
canal containing blood and lymphatic
vessels and nerves
Volkmann’s canals:
Nutrient running at right angle to the Haversian canals; contain blood vessels and nerves of bones
Mechanisms of Calcification - Process done by osteoblasts:
1- Osteoblasts secrete the new organic matrix, non-mineralized, called osteoid
2 - Osteoblasts secrete factors (alkaline phosphatase, glycoproteins such as osteonectin and osteocalcin, calcium salts…) allowing the subsequent mineralization of the matrix
3 - Osteoblasts become trapped in their own mineralized matrix: become osteocytes residing in lacunae
4 - Osteocyte keeps a limited ability to secrete and reabsorb bone in its lacuna, allowing some bone turnover to occur
Mechanisms of Calcification - depend on factors secreted by osteoblasts in the matrix:
- Alkaline phosphatase promotes accumulation of inorganic phosphate in the osteoid, this is a point of saturation where calcium phosphate precipitates
- High affinity calcium binding proteins (osteonectin, osteocalcin)
- Matrix vesicles containing pyrophosphate and enzymes that inhibit calcification and allow phosphate release
Bone Remodeling:
- Balance between bone deposition and resorption
- Bone deposition : Ensure high vascularity - Trapping of new vessels during bone deposition and anastamose of trabeculae
- Bone Resorption: Allows formation of canals/marrow cavity
- Required to maintain shape in growing bones: skull/long bones
- Balance deposition/resorption allows bone response to mechanical stress, adaptation to movement/strain
- Osteons constantly remodeled
- Help maintain calcium homeostasis (via PTH and calcitonin)
Diseases due to unbalance between bone deposition & resorption:
- Osteoporosis: resorption > deposition → bone mass loss (elderly)
- Osteopetrosis: deposition > resorption → bone mass excess marble bone disease, due to abnormal osteoclasts
Nutritional factors:
Vitamin C • deficiency: Scurvy, altered collagen formation, fragile bone, fractures
Vitamin D • deficiency: Impaired intestinal absorption of calcium
In infant, Rickets, skeletal deformities (bowing legs, knock-knee)
In adult: osteomalacia, weak bones, fractures
• excess: abnormal calcification of soft tissues, toxic
Vitamin A • deficiency: in fetus, skeletal deformity, in children, slow bone growth, small skull, CNS damage.
Childhood, premature epiphyseal closure, small stature
• excess: slow cartilage growth and accelerated ossification
Hormonal factors:
Growth hormone:
• deficiency in childhood, pituitary dwarfism
• excess in childhood, gigantism
• GH excess in adult (pituitary tumor), acromegaly (enlargement of the skeleton)
Sex Steroids:
• Influence time of appearance of ossification centers during bone development and closure of epiphyses:
- Precocious (early) sexual maturity or tumor, short stature
- Delayed puberty (extreme exercise), sex hormone deficiency, tall stature
Hyperparathyroidism: excess PTH, excess bone resorption, bone mass loss, fragile bones, excess circulating calcium, deposit in soft tissue (kidney)
Bone Growth: Reversible differentiation
vascular environment / growth factors
Primary (woven/immature) bone formation: Intramembranous ossification
Direct; Mesenchymal Condensation & direct mineralization by osteoblasts
i.e. differentiation of mesenchymal cells into osteoblasts then osteocytes
Primary (woven/immature) bone formation: Endochondral ossification
Indirect; Ossification of a preexisting cartilage model
i.e. replacement of cartilage with osteoblasts & osteocytes
Intramembranous ossification:
- Occurs in areas of vascularized mesenchyme
- Flat bones (membrane bones)
- Growing short bones - Periosteal bone collar of long bones (bone thickening)
- Flat bones (membrane bones)
- Differentiation of mesenchymal precursor cells to osteoblasts, leading to bone deposition and mineralization
Intramembranous ossifcation: sequence of events
- Mesenchymal condensations
- Appearance of blood vessels
- Differentiation into osteoblasts:
primary ossification center - Mineralization by Osteocytes
- Spicules/trabeculae formed
- Interweaving of trabeculae:
Spongy bone & Marrow cavities
Endochondral Ossification: short & long bones - Prenatal growth
- Hyaline cartilage model (precursor, anlagen)
- Subperiosteal bone collar around cartilage (Intramembranous) Prenatal growth
- Primary endochondral bone (cartilage replacement)
Endochondral Ossification: short & long bones - Postnatal growth
-Growth of epiphyseal plates
-Marrow cavity extends
Mature bone (compact at diaphysis/spongy at epiphysis)
Step 1: Prenatal growth, hyaline cartilage model & subperiosteal bone collar
- Embryonic mesenchymal condensation
- Differentiate into chondroblasts
- Small hyaline cartilage model (anlagen)
- Capillaries penetrate perichondrium at mid-portion of cartilage model, mesenchymal cells become osteogenic, periosteum
- Formation of subperiosteal bone collar by intramembranous ossification (i.e. mesenchyme differentiates into osteoblasts)
Step 2: Prenatal growth, cartilage degeneration & primary ossification center
- Chondrocytes in midregion of cartilage proliferate in long stacks, hypertrophy, matrix calcifies, cartilage degenerates, forms calcified trabeculae & spaces
- Blood vessels from periosteal bud (cluster of blood vessels and perivascular tissue from periosteum) enter calcified cartilage, bringing osteoprogenitor cells, osteoclasts and bone marrow stem cells
- Endochondral ossification (cartilage replacement) with osteoprogenitors, osteoblasts.
Primary bone formed on calcified cartilage remnants & bone marrow formation (D):
Primary ossification center (diaphyseal)
Step 3: Postnatal growth, formation of secondary ossification centers
- Formation of a secondary (epiphyseal) ossification center in one of the epiphysis (E) following same mechanism as for primary center (invasion by epiphyseal artery, primary bone & marrow formation)
- Diaphysis: bone collar grows toward epiphyses, Spongy bone formed in center, Marrow cavity enlarges
-Epiphysis: growth of epiphyseal growth plate, bone growth in length until adulthood. Regulated by GH/IGF1 (somatomedins)
5 distinct zones in epiphyseal cartilage
-Spongy bone replaces woven bone at the
first epiphysis. Articular cartilage remains around the epiphysis
Second secondary ossification center starts at second epiphysis
Step 4: Postnatal growth until adulthood: growth plate closure
- The first epiphysis matures (G): growth plate closes and progressively disappears (16-20 y.)
- The only remaining cartilage in the epiphysis is the articular cartilage
- Growth of second epiphyseal plate
- Expansion of central marrow cavity
- Bone collar becomes compact boneAdult bone (H):
- Epiphyseal cartilage plate no longer present
- Compact bone at diaphysis
- Spongy bone at epiphysis
- Marrow space contains yellow (adipose) marrow
- Periosteum surrounds shaft (no at articular joint)
- Articular cartilage without perichondrium
Bone growth & remodeling of long bone
- Epiphyseal plate provide growth in length
- Epiphyseal spicules get incorporated into diaphysis
Unstable/mobile fractures repaired by endochondral ossification:
Fracture, interruption of blood supply, necrosis & blood clot
↓ oxygen supply, macrophages/fibroblasts, fibrous tissue
Periosteal osteoprogenitors become chondrogenic
Cartilage bridge formed at site (callus) as early as 4 days after break
Blood vessels reappear, osteogenic potential
Primary bone forms as early as 2 weeks after break, then secondary bone
mechanical stress & muscular activity necessary to restore bone shape
Fractures in non-weight bearing bones or hair line fracture can be repaired directly by
intramembranous ossification
Joints : arthroses
Synarthrose: permit little or no movement
- Syndesmosis (fibrous joints): joined by dense connective tissue (cranial sutures in young)
- Synostose: immobilized, fused bones (old skull bones)
- Synchondrose (primary cartilaginous joint): bones joined by hyaline cartilage (rib/sternum)
- Symphysis (secondary cartilaginous joint): bones joined by fibrocartilage (pubic symphysis, intervertebral discs)
Diarthrose (synovial/articular joint)
- movable joints between long bones
- articular cartilage (no perichondrium)
- Synovial fluid
- Capsule (2 layers)
outer membrane: fibrous
inner membrane: synovial membrane
A cell: Phagocytic
B cell: secrete synovial fluid - Reinforced by ligaments
- Stabilized by muscles and tendons
- Ligaments and tendons attached to bone by Sharpey’s fibers
