Bone Growth and Collagen

Endochondral Ossification: (summarized from Dellmans Veterinary Histology)


  1.  Embryological long bone
  1. Formed initially as Hyaline cartilage (Type II collagen)
  2. Eventually replaced by Bone (Type I collagen)
  1. Chondrocytes proliferate and produce ECM
  2. Chondrocytes Hypertrophy and the ECM becomes thin
  3. Chondrocytes release matrix vesicles which promote calcification of the cartilage matrix
  4. Calcification prevents the chondrocytes from receiving nutrition and they die
  5. Perichondrium is invaded by new vessel growth
  1. Essential for differentiation into osteoblasts
  1. Osteoprogenitor cells differentiate into osteoblasts
  1. Form a thin shell of bone around the cartilage model by intramembranous ossification (Periosteal band or Bony Collar)
  1. Blood vessels invade into the area of degenerating hypertrophied chondrocytes
  1. Osteoprogenitor cells from periosteun, pericytes, and undifferentiated mesynchymal cells all accompany the BV
  1. Osteoblasts surround calcified cartilage and secrete osteoid and later produce matrix vesicles that promote mineralization of the osteoid
  1. This forms bony trabeculae with cartilage cores
  1. The bone in the primary center of ossification is resorbed by osteoclasts forming the marrow cavity which gets filled with hemopoietic tissue from the undifferentiated mesenchymal cells
  2. Secondary ossification centers form at the epiphyses of long bones
  1. Cartilage canals containing blood vessels and nerve fibers supply the epiphysis but do not cross the physis or the articular cartilage
  2. The capillaries from glomerular structures around which the chondrocytes hypertrophy, then degenerate, and calcify
  1. Physeal cartilage lasts until sexual maturity then is replaced by bone
  2. Growth in bone length
  1. Reserve Zone (resting zone)
  1. Small chondrocytes dispersed in an irregular patter
  2. Nourished by capillaried from the epiphysis
  3. Matrix vesicles are formed
  1. Zone of Proliferation
  1. Chondrocytes are somewhat larger and form narrow columns
  2. They continue to synthesize ECM
  3. ECm separates each cell from its neighbor
  1. Zone of Hypertrophy
  1. Cells increase in size and begin to accumulate calcium
  2. Cellular calcium is released into the matrix and matrix vesicles take it up
  3. Alkaline phophatase and neutral proteases released from matrix vesicles cause local increase of phosphate
  4. Accumulation of calcium in the vesicles and in crease in phosphate leads to mineralization of the matrix
  5. The last 2-3 chondrocytes in the column are bordered by a wall of mineralized matrix, but the transverse septa between the chondrocytes don’t mineralize
  1. Zone of Resorption
  1. Metaphyseal capillaries make U-turns and return to medullary cavity
  2. Capillary loops and perivascular connective tissue invades the lacunae of degenerating hypertrophic chondrocytes
  1. Zone of Ossification
  1. Osteoblasts differentiate from cells accompanying the invading capillaries
  2. Theses cells deposit osteoid on the calcified walls of the chondrocytic lacunae
  3. This results in trabeculae of bone with mineralized cartilage cores (primary spongiosa)
  4. Osteoclasts line the primary trabeculae for a short distance into the metaphysis
  5. Osteoclasts resorb bone from the surface of the trabeculae and reduce their numbers
  1. Metaphyseal bone
  1. Primary spongiosa decreases
  2. Trabeculae are composed of lamellar bone without cartilage cores (secondary spongiosa)
  1. Growth in Width and circumference (Intramembranous)
  1. The original Bony Collar becomed remodeled to compact bone
  2. The periosteum forms new bone and so increases bone width
  3. Endosteum resorbs bone and so increases the medullary cavity
  1. Cortical bone
  1. Primary osteons are concentric layers of bone formed around periosteal blood vessels
  1. Lack cement lines
  2. Often have 2 or more BV in their central canal
  1. These are gradually replaced by more orderly secondary osteons
  1. Surrounded by basophilic cement lines composed of mineralized matrix deficient in collagen
  1. Interstitial lamellae lie between secondary osteons in irregular shapes
  2. Inner and Outer circumferential lamellae
  1. As bone growth slows and appositional growth adds more layers to both the periosteal and endosteal surface the surface becomes smoother
  1. Modeling and remodeling
  1. Diaphysis
  1. Periosteal bone forming
  2. Endosteal bone resoprtion
  1. Metaphysis
  1. Periosteal bine resorption
  2. Endosteal bone formation
  1. Remodeling is cyclical
  1. Resoprtion occurs followed by bone formation
  1. Cortical bone
  1. Cortical remodeling units
  1. cutting cone
  1. osteoclasts
  2. osteoblasts
  3. glomerular capillary
  1. Reversal zone
  1. the demarcation of bone resoprtion and bone formation
  1. Closing cone
  1. osteoblasts close the newly excavated osteon by adding centripetal layers of lamellar bone inward from the cement line boundary
  1. Spongy bone
  1. remodeling occurs at the endosteal surface of the trabecula
  2. Osteoclasts resorb bone
  3. Osteoblasts form new bone


  1. Woven bone:  Also called immature bone.  The form of bone found in the primary spongiosa as a result of endochondral ossification.  Woven bone becomes remodeled to mature bone.  The terms woven and lamellar can apply both to cortical and cancellous (trabecular) bone. (Found in both cortical bone primarily during development but also when forming new osteons).
  2. Lamellar bone:  Mature bone, recognized by the presence of cementing lines (basophilic lines of mineralized matrix with little osteoid) (see below for types of cementing lines or Jubb and Kennedy vol 1 p9). Found in both cortical and spongy (cancellous, trabecular) bone.
  3. Cortical bone: Compact bone, formed of subunits called osteons.  The center of an osteon is a blood vessel with osteoclasts, osteoblasts and mesenchymal cells.
  1. Mature osteons are surrounded by circular layers of lamellar bone called osteonal lamellae.
  2. The network of blood vessels traversing the bone are called Haversian systems.  Osteocytes are surrounded by bone on all sides and communicate with eachother through intercellular canaliculi.  Mature cortical bone is lined by periosteum on the outside and lined inside by endosteum and osteoblasts.
  3. The inner layer of cortical bone is made of flat sheets of lamellar bone called the inner circumferential lamellae
  4. The outer surface just beneath the periosteum is made of flat sheet (not in osteons) of lamellar bone called the outer circumferential lamellae.
  1. Cancellous or trabceular bone:  Bone spicules in the medullary cavity, lined by endosteum and osteoblasts and osteoclasts
  2. Resting lines:  cementing lines formed of normal bone growth by the cyclic action of osteoblastic bone deposition and a period of inactivity
  3. Reversal lines:  cementing lines formed by bone remodeling.  Osteoclastic bone resorption removed old bone, and osteoblastic bone deposition lays down new bone.  These tend to be scalloped lines.  
  4. Haversion canal: The central canal in the osteon, carrying blood vessels, lymphatics, and myelinated nerve fibers with coonective tissue stroma.  Central canals are connected to eachother by Volkmanns canals (also called perforating canals)

  1. Fibrillar Collagen (taken from Robbins)
  1. Type 1
  1. Most common
  2. Bone. Tendon, skin
  3. Osteogenesis imperfecta
  4. Ehlers danlos- arthrochelasias type
  1. Type II
  1. Cartilage
  1. Type III
  1. Hollow organs and soft tissue
  2. Vascular Ehlers Danlos
  1. Type V
  1. Soft tissues
  2. Blood vessels
  3. Fetal tissues
  4. placenta
  5. Classical Ehlers Danlos
  1. Type IX
  1. Cartilage
  2. Vitreous
  1. Type XI
  1. Hyaline Cartilage
  1. Basement Membrane
  1. Type IV
  1. Also with Laminin
  1. Other
  1. VII
  1. Anchoring fibrils at dermal epidermal junction- links Type IV to collagen beolw
  2. Dystrophic epidermolysis bullosa
  1. IX
  1. Cartilage, IV disks
  1. XVII
  1. Transmembrane collagen in epidermal cells