Test 3 Bone

Inorganic Components of Bone

• 65% bone weight

• Hydroxyapatite crystals

• Calcium and Phosphate materials

Osteoid

• 35% bone weight

• Collagen I

• Ground substance GAGs, Proteoglycans, Multiadhesive glycoproteins.

Osteoprogenitor cells

• Located in endosteum and periosteum

• Spindle shaped

• Produce osteoblasts

Osteoblasts

• Synthesize organic components (osteoid)

• Located on surface of bone

• Cuboidal, joined with gap junctions

Bone Lining Cells

• Located in endosteum and periosteum

• Derived from osteoblasts

Osteocytes

• Derived from osteoblasts

• Located within lacunae between lamellae

• Canaliculi

• Maintenence of bony matrix

• Mechanotransduction - respond to mechanical forces

Osteoclasts

• Large branched cells

• Bone resorbing

• 2-50 nuclei

• Surface of bone, Howship lacunae

• Acidophilic

• Secrete acid and collagenase

Osteoclast Differentiation

• Dependent on stromal cells

• RANK/RANKL

• OPG is a decoy receptor produced by osteoblasts to decrease osteoclast development (covers RANKL)

Regions of Osteoclasts

1. Ruffled border - near bottom, bone resorption, many lysosomes and ATP dependent proton pumps

2. Clear zone - seals cell from microenvironment between osteoclasts and bone surface

3. Basolateral zone - exports digested bone material by exocytosis

Hormones affecting Bone

Parathyroid hormone → osteoblast → +M-CSF and +RANKL

• The addition of these hormones promote osteoclasts development, which in turn release calcium in blood

Thyroid C-cells → Calcitonin → suppresses osteoclasts

Estrogen and Bone

Estrogen produces cytokines that produce osteoblasts and marrow stromal cells. Without estrogen, these cells are not produced as efficiently and cause bone erosion.

Periosteum

• Dense regular or irregular CT

• Located on outer surface of bone

• Sharpey’s fibers - connect to bone

• 2 Layers: Outer fibrous, inner cellular

• Function: supply blood and osteoblasts for bone repair and growth

Endosteum

• CT lining internal cavity of bone

• Reticular CT

• Function: supply blood and osteoblasts for bone repair and growth

Classification of Bone

1. Architecture - spongy/cancellous or compact/dense/cortical

2. Fiber organization - lamellar/non-lamellar

3. Histogenesis - primary/immature, secondary/mature

Primary Bone

• Higher proportion of osteocytes

• More ground substance

• Non-lamellar, always spongy

Secondary Bone

• Spongy or compact

• Eosinophilic

• Higher mineral content and stronger

• Lamellar

Intramembranous Ossification

1. Mesenchyme forms osteoblasts

2. Primary ossification center with osteoblasts lay down matrix, followed by calcification to form spicules

3. Islands of developing bone fuse to form spongy bone, spicules enlarge

4. Becomes vascular, forms marrow, periosteum and endosteum.

(Mostly flat bones)

Endochondral Ossification

1. Zone of reserve cartilage

2. Zone of proliferation

3. Zone of hypertrophy

4. Zone of calcified cartilage

5. Zone of resorption/ossification

6. Growth is extended toward epiphysis (ends of bone)

Ossification Centers

1. Primary - center of diaphysis

2. Secondary - within epiphysis

3. The only cartilage that remains after ossification is articular cartilage and epiphyseal plate

Mineralization of Extracellular Matrix

• Matrix vesicles are secreted by osteoblasts that are stimulated by elevated calcium and phosphates.

• Crystallization of CaPO4 occurs in vesicle.

• Crystals form hydroxyapatite in matrix surrounding osteoblasts.

Indirect Bone Healing

1. Fracture and bone necrosis. Fibroblasts and capillaries form clots/granulation tissue (procallus)

2. Procallus into fibrocartilage form (soft callus)

3. Soft callus replaced by primary bone (hard callus)

4. Primary bone replaced by secondary bone

Vitamins associated with Bones

• Vitamin D - calcification, intestinal absorprtion of calcium

• Vitamin A - bone health, deficiency suppresses endochondral growth and leads to fragility and fractures.

• Vitamin C - essential for collagen synthesis

Bone Diseases

• Rickets/Osteomalacia - calcium deficiency due to lack of Vitamin D

• Osteoporosis - insufficient mineralization, osteoclast activity exceeds osteoblast deposition

• Scurvy - lack of vitamin C, lack of collagen leads to a matrix that will not calcify

• Osteopetrosis - increase in bone density due to defective osteoclasts. Bones are fragile, over-mineralization.

Hormones and Bone

• Parathyroid - osteoblast reabsorb bone, release calcium, RANKL+

• Calcitonin - inhibits bone reabsorption, lower blood calcium

• Growth Hormone - growth of epiphyseal cartilage. Hypersecretion = giantism or acromegaly if child, hyposecretion = dwarfism

• Thyroid Hormone - lacking = failure of bone growth and dwarfism