Cartilage and Bone

o  Capsule covering of cartilage
§  Dense Irregular connective tissue.
§  Allows for blood, nerve & lymph vessel passage

§  Surface of cartilage (derived from mesenchymal cells)
§  Actively secreting cartilage matrix (abundant RER & Golgi).
§  Responsible for appositional growth.
§  Highly hydrated

Embedded in Cartilage Lacunae
Produce and maintain ECM
§  Large, Rounded. Capable of mitosis.
§  Large, Euchromatic nucleus.
§  Produce GAGs and Collagen type II
§  Dividing chondrocytes form clusters called isogenous groups.
§  Actively dividing: Completely surrounded in matrix. Fairly actively secreting material. Capable of mitosis.
Push matrix to side when divided.

Collagen Type II
·  Thin fibrils,
  no fibers or bundles.
· Banding in TEM.
·  Mechanical stability and tensile strength.

GAGs and proteoglycans
  ·  Hyaluronic acid: Long. Bind non-covalently through link protein to proteoglycans form giant complexes.
Large (-) charge
Bind water forming a hydrated gel. ·  Chondroitin Sulfate: Covalently linked to core proteins to form proteoglycans.

Multiadhesive Glycoproteins
Cross link collagen and proteoglycans
Attach ccytes to matrix

o  Not uniform.
o  Matrix around lacunae w/ chondrocytes has fewer collagen fibers and is richer in GAGs.
    §  Territorial matrix: Stains intensely w/ basic dyes (hematoxylin)
o  Interterritorial matrix: Between lacunae: Stains less intensely w/ basic dyes.

Hyaline
Elastic
Fibrocaratilage

§  Well developed perichondrium (dense irregular connective tissue).
§  Perichondrium Absent from articular cartilages and epiphyseal plates.
§  Matrix composed primarily of collagen type II, GAGs and proteoglycans.
§  No visible fibers.
§  Chondrocytes in lacunae, arranged into isogenous groups.

§  Widely distributed.
Forms embryonic skeleton.
Serves as template for bony skeleton.
Forms articular surfaces of movable joints, epiphyseal plates, costal cartilages, and supports respiratory systrem (nose, trachea, bronchi, larynx).
§  No perichondrium on top of hyaline cartilage in joints.
Epiglottis is elastic cartilage.

§  Well developed-perichondrium.
§  Use Orsin stain, see lots of wispy, coiled elastic fibers.
§  Matrix composed of Collagen type II, Gags, proteoglycans and elastic fibers (visible in light microscope.
§  Matrix does not ossify.
§  Chondrocytes located in large, istended lacunae.

§  Ear auricle, external auditory canal walls, Eustachian tube, epiglottis.

§  Hybrid between hyaline cartilage and dense irregular connective tissue.
§  No perichondrium.
§  Can see bundles of collagen type I in light microscope
§  Matrix composed of collagen type II, type I, GAGs, and proteoglycans.
Coarse fibers and bundles of collagen type I can be visualized in light microscope.
§  I brings tensile strength. II brings elasticity.

§  Found in intervertebral disks, pubic cartilage, and sternoclavicular and temporomandibular joint.

o  Chondrosarcoma: Malignant proliferation of cartilage.
§  Wide age range
§  Male predominancy
§  Pelvis, proximal femur, proximal humerus.
§  Slow Growing tumor.
§  Abundant cartilaginous matrix.

·      Mineralized extracellular matrix.

·      One of hardest tissues in body.

·      Formed by collagen fibers, ground substance, and cells.

·      Withstands compression, deformation, and stress

·      Diffusion limited due to mineralized ECM.

·      Vascular tissue w/ blood and lymph vessels running through it

      o  Heals faster than cartilage.

Outer shell: Compact/Cortical bone
Spongy or trabecular bone forms: Spicules/Trabeculae on inner side of bone; extends to marrow cavity
o  External surface covered with periosteum. (dense irregular connective tissue) §  Two layers: External fibrous layer (collagen fibers), Internal osteogenic layer (osteoprogenitor cells). o  Internal marrow cavity lined with endosteum (thin layer of connective tissue w/ osteoprogenitor cells)

(filled with reticular (Hemopoietic) connective tissue or fat (yellow marrow).

Organic and Inorganic

Dense Connective Tissue

o  Organic matrix: Dense irregular connective tissue
§  Large collagen type I bundles (tensile strength)
§  GAGs (chondroitin sulfate, keratan sulfate), bind covelantly to proteins to form large proteoglycan aggregates. Attach non-covalently to hyaluronic acid.
§  Multiadhesive proteins. (bind organic to inorganic components)
§  Little ground substance in bone matrix.

§  Calcium phosphate (Ca(PO4)2), exists as hydroxyapatite crystals (Ca10(Po4)6(oh)2). §  Calcium Carbonate, Mg, Na, K.

Osteoprogenitor Cells
OsteoBlasts
Osteocytes
Osteoclasts

§  Periosteum and endosteum. §  Derived from mesenchymal cells. §  Differentiate into osteoblasts.

§  Principal bone-forming cell §  Secretes bone matrix. §  Only found at boundary b/w bone and adjacent tissue. §  Versatile secretory cells. §  Secrete Collagen Type I, and bone matrix proteins. §  Responsible for calcification of bone. §  Appositional growth. §  Cuboidal cells with basophilic cytoplasm well developed RER and Golgi (Active). §  Squamous cells (inactive)

§  Osteoblasts trapped in matrix. §  Housed in lacunae within calcified bone matrix. §  Canaliculi connect adjacent lacunae. §  Maintain bone, deposit and mobilize calcium from matrix.

§  Large, multinucleated cells with acidophilic cytoplasm.
§  Derived from bone marrow, not mesenchyme.
§  Resorption of bone.
§  Attached to bone via actin-rich area: clear zone.
§  Direct contact with bone is ruffled border.
§  Secrete H+ ions, collagenase, and lysosomal enzymes.
§  Promote digestion of collagen and dissolving calcium phosphate crystals.
§  Depression in matrix caused by osteoclasts : Howship’s lacunae

OsteoSarcoma
Osteoid Osteoma
Paget's Disease

§  Production of Osteoid by malignant cells. ~20% of bone malignancy, prevalent in teenagers. Occurs at sites of rapid bone growth. Distal femur, proximal tibia, proximal humerus. Highly metastatic.

§  Small, benign tumor. Occurs anywhere in appendicular skeleton or spine. Acute night pains. §  Composed of primary bone with osteoblasts surrounding osteoid.

§  Enlarged and deformed bones.

§  Problems with secondary bones.

§  Stages

·      Increased activity of osteoclasts. Results in bone resorption.

·      Deposition of irregular patches of primary bone.

·      New bone is more fragile and prone to fractures.

Constantly being remodeled

Primary/Woven bone §  Immature type of bone laid down when bones first formed or repaired. Collagen fibers irregular and interwoven.

Secondary/Lamellar bone ·      Collagen fibers organized into layers, lamellae. ·      Stronger than woven bone. ·     
Structural unit: Osteon

o  Haversian system. o  Concentric cylindrical structure formed around central canal o  Runs parallel to long axis of bone. o  Haversian canal contains neurovascular bundle surrounded by connective tissue. o  Lined with osteoblasts.

·      Canal surrounded by concentrically arranged lamellae. Collagen fibers within each lamella have same orientation. Fibers of adjacent lamella are 90 degrees to each other. Likened to plywood. ·      Lacunae w/ osteocytes located b/w lamellae. Lacunae connected by canaliculi ·      Volkmann’s canals: Transverse channels in mature bone. ·      Blood vessels and Nerves travel from bone periphery to haversion canals run through this.

(remnants of old haversian systems), partially obliterated by new osteons.

Laid down by osteoblasts formed from periosteum on the outer side of bone (more active).

Formed on inner surface of bone by osteoblasts derived from endosteum.

Intramembraneous ossification
Endochondral Ossification

§  Bones of skull. §  Formed directly from connective tissue. §  Mesenchymal cells differentiate into osteoblasts. §  Secrete bone matrix and form network of spicules and trabeculae. §  Initial osteogenesis at Primary Ossification Center. §  Trapped osteoblasts become osteocytes.

§  Long and short bones. §  Bone formed by replacement of cartilaginous template with bony tissue. §  Primary ossification center located on diaphysis of long bone

§  Secondary ossification centers located in epiphyses of long bones.

·      Responsible for formation of articular cartilage and epiphyseal growth plate.

·      Miniature hyaline cartilage model formed. ·      Model grown serving as a structural scaffold for bone development. ·      Cuff of bone formed around middle of cartilage. ·      Perichondrioum of this part invaded w/ blood vessels and turns into periosteum. ·      Bony collar (through intramembranous ossification) established around diaphysis. ·      Chondrocytes stop receiving nutrients and die.

·      Blood vessels and osteoprogenitor cells migrate into degenerated cartilage.

·      Osteoprogeinitor cells differentiate into osteoblasts, line surface of calcified cartilage, start secreting bone matrix.

·      Remodeling results in replacement of calcified cartilage by bone matrix.

Real People Have Cool Oaks

o  Zone of Reserve cartilage: hyaline cartilage w/ chondrocytes.
o  Zone of proliferation: Rapid tissue growth, division of chondrocytes ( columns of stacked cells/ isogenous groups) parallel to long axis of bone.

Zone of hypertrophy (swollen chondrocytes)

o  Zone of calcification (chondrocytes lost by apoptosis), accompanied by calcificaiton of cartilage matrix.

o  Zone of ossification: Appearance of bone tissue, synthesized by osteoblasts over the layer of calcified cartilage.