2 types of Bone formation1) Intramembranous Ossification Development of ossification Center Mesenchyme cells crowd together they will differentiate into osteoprogenitor cells Osteoprogenitor cells will then differentiate into osteoblasts Osteoblasts will secrete matrix until they are surrounded by itCalcification Once osteoblasts are surrounded by extracellular matrix they then become osteocytes In a few days Calcium and other inorganic mineral salts will deposit in the extracellular matrix This will calcify the matrixFormation of Trabeculae As bone extracellular matrix forms it develops into trabeculae The trabeculae fuse with one another around blood vessels and arteries Development of Periosteum Messechymal cells will condense together at the periphery of the bone to form the periosteum Eventually the periosteum will deposit compact bone around the outside the bone 2) Endochondral Ossification Development of Cartilage Model Mesenchyme crowd together in general shape of bone they then differentiate into chondroblasts Chondroblasts secrete cartilage extracellular matrix, producing cartilage model Pericondrium develops around modelGrowth of Cartilage Model Model grows in 2 ways Appositional Growth: Occurs in the perichondrium, the chondroblast secrete more matrix and this cartilage model grows in width Interstitially: chondroblasts experience mitosis in the center of the cartilage model (this is how the model grows in length) The cells within the model will then stop dividing and will begin to grow in size (hypertrophy) due to the lack of nutrients getting to the cells Some will grow so big that they will burst and spill their intracellular contents into the matrix, this will change the pH or acidify the matrix This acidity will draw Calcium to the matrix (which will calcify the matrix) Calcium is an inhibitor of diffusion and thus other cells around will go through the same process of (hypertrophy, burst, die, acidify, calcify) Development of Primary Ossification Center The nutrient artery will then penetrate the perichondrium through the nutrient foramen and will bring osteoprogenitor cells into the diaphysis region as well it will bring blood Once the artery has been brought in the osteoprogenitor cells will differentiate into osteoblasts The osteoblasts will then lay down bone extracellular matrix over the remnants of calcified cartilage (forming spongy trabeculae) Primary ossification spreads from center outwards Development of Medullary Cavity The nutrient artery will also bring in osteoclasts into the diaphysis along with the osteoblasts When compact bone is thick enough to support the mechanical stress osteoclasts will absorb the trabecular bone on the inside of the diaphysis to form the medullary cavity Development of Secondary Ossification Center This process is much like primary ossification Chondrocytes will divide, grow, burst, die, acidify and the matrix will calcify The branches of the epiphyseal artery will enter the epiphysis bringing in osteoprogenitor cells and blood as well as osteoclasts Osteoblasts will turn cartilage model into bone tissue In this case osteoclast will not absorb trabeculae (there will be no medullary cavityDevelopment of Articular Cartilage Not the entire epiphysis will be turned to bone Around the edges will stay cartilage (this forms the articular cartilage) As well in b/w the epiphysis and the diaphysis will stay cartilage (this is the growth plate) Growth in length Bones grow in width through interstitial growth, this type of growth occurs within a cartilage model It happens when the chondrocytes undergo mitosis In developed bones this type of growth cannot happen in the bone tissue It occurs in the metaphysis region in the epiphyseal plate (this plate is made up of hyaline cartilage) The epiphyseal plate consists of 5 zones which aid to growth in length The zone of resting cartilage: consists of small chondrocytes, this zone does not actually aid in the growth process, but it does attach the epiphyseal plate to the epiphysis The zone of proliferating cartilage: Chondrocytes in this zone undergo rapid cell division. This is the zone where interstitial growth occurs. The chondrocytes in this zone look like stacks of coins. The zone of hypertrophic cartilage: Chondrocytes in this zone stop dividing and undergo growth in size. The chondrocytes are still arranged in stacks. The zone of calcified cartilage: Chondrocytes are mainly dead here because the extracellular matrix has calcified. The zone of bone deposition: Osteoclasts dissolve the calcified cartilage, and osteoblasts and capillaries from the diaphysis region invade the area. The osteoblasts lay down bone extracellular matrix, replacing the calcified cartilage by the process of endochondral ossification. Growth in Width (appositional growth) At bones surface the periosteal cells differentiate into osteoblasts Secrete collagen fibers and other organic molecules that form bone extracellular matrix Once osteoblasts are surrounded by extracellular matrix they become osteocytes This process forms bone ridges on either side of the periosteal blood vessel The ridges slowly enlarge and create a groove for the blood vessel The ridges will fold together and fuse, the groove becomes a tunnel that encloses blood vessel The former periosteum is now the endosteum and it lines the tunnel Osteoblasts in the endosteum deposit bone extracellular matrix, forming new concentric lamellae This formation proceed inward, toward periosteal blood vessel In this way the tunnel fills in and the new osteon is created As osteon is forming, osteoblasts under the periostum deposit new circumferential lamellae, further increasing the thickness of the bone. As additional periosteal blood vessels become enclosed to form osteons the growth process continues

**As bone is being deposited on the outside osteoclasts are absorbing bone tissue in the medullary cavity, making the medullary cavity bigger while increasing the thickness**