 In this video, I will describe the process of bone ossification, comparing intramembranus ossification and endocondral ossification, and then describe the process of bone growth in length, known as interstitial bone growth, as well as the process of bone growth in width, also known as oppositional bone growth. The process of ossification is the production of bone from another tissue, so osseous tissue is a replacement tissue that's formed from a pre-existing tissue. The mechanism of intramembranus ossification produces bone from a fibrous connective tissue such as the dermis. Intramembranus ossification is the mechanism that leads to the production of most of the flat bones of the cranium, for example the parietal bone, frontal bone, portions of the temporal and occipital bones are all formed from intramembranus ossification of the overlying dermis. During intramembranus ossification, connective tissue stem cells differentiate into osteogenic cells that form osteoblasts. During fetal development, there's a type of stem cell known as mesenchymal cells that are a stem cell that can form a wide diversity of different connective tissue cell types. Mesenchymal cells differentiate to form osteogenic cells and then those osteogenic cells further differentiate to produce osteoblasts. Osteoblasts then start to secrete osteoid, that is the osteoblasts secrete collagen fibers producing the matrix of protein fibers that give the tensile strength and structure for bone. However, the osteoid is not finished until after it becomes mineralized to form the hardened osseous tissue. So the next step of intramembranus ossification is calcification of the osteoid in order to form bone spicules. When these bony spicules continue to grow as osteoblasts produce more osteoid that becomes calcified, these spicules eventually grow and merge together surrounding blood vessels. This network of osseous tissue surrounding blood vessels forms the characteristic branching strep like plates of osseous tissue known as trabeculae that are characteristic of spongy bone. Following the formation of this basic spongy bone that is entrapped blood vessels, the final step of intramembranus ossification will be to form a periosteum and a layer of compact bone that surrounds the deep spongy bone. In this process, the connective tissue surrounding the spongy bone differentiates forming periosteum as mesenchymal cells differentiate into osteogenic cells and those osteogenic cells differentiate into osteoblasts. Then the osteoblasts secrete osteoid that becomes calcified forming a structure of compact bone that is surrounding the spongy bone. In contrast to intramembranus ossification, endocondral ossification forms bone from a cartilage model. The model of bone that's first formed during fetal development is a blueprint of the bone's basic shape produced out of hyaline cartilage tissue. As the hyaline cartilage model grows deep within the cartilage, chondrocytes start to become starved for nutrients. As the matrix of the cartilage becomes calcified, this makes it more and more difficult for nutrients to reach the chondrocytes deep within the hyaline cartilage model. These chondrocytes then start to die and as the chondrocytes die leaving a cavity deep within the cartilage model, blood vessels will start to grow into the center of the cartilage model. As this is occurring, cells in the outer layer of the cartilage model, which were the cells of the pericondrium, start to be replaced with cells of the periosteum. Some of these cells, the osteogenic cells and osteoblast cells will also migrate with the blood vessels deep into the center of the cartilage model where chondrocytes have died leaving a space. Osteoblasts will then start to secrete osteoid in the center of the cartilage model and that osteoid will become calcified forming osteos tissue. This region where osteos tissue first forms deep within the hyaline cartilage model is known as the primary ossification center. As the primary ossification center grows, osteoclasts will start to resorb osteos tissue from the center to generate a medullary cavity. At the same time, chondrocytes near the ends of the hyaline cartilage model start to become starved for nutrients and die leaving space in the ends of what are forming the epiphyses of a long bone. In a similar process to the formation of the primary ossification center, blood vessels grow into the ends of the long bone carrying osteoblasts into the end of the long bone that will start to produce osseous tissue of the secondary ossification center. Primary ossification center is produced at each end of a long bone and the primary ossification center is in the middle of the long bone, so the secondary ossification centers are within the epiphyses and the primary ossification center is within the diaphysis. But there is hyaline cartilage still separating the epiphyses from the diaphysis and that hyaline cartilage becomes the epiphysial growth plate that enables interstitial bone growth so that the bone can become longer through adolescence. Interstitial bone growth also known as longitudinal bone growth is the mechanism through which a long bone increases in length. This occurs at the epiphysial growth plate where there is a layer of hyaline cartilage between the epiphyses and the diaphysis of a long bone. At the region of the epiphysial growth plate furthest from the diaphysis is the reserve zone of hyaline cartilage. Moving towards the diaphysis, the next zone is the proliferative zone where chondrocytes are actively dividing through mitosis, a cell division that produces more chondrocytes to help increase the length of the long bone making the epiphysial growth plate larger. Then as we move closer to the diaphysis we enter the zone of maturation and hypertrophy where chondrocytes become larger and the matrix surrounding the chondrocytes gradually starts to accumulate calcium. As the matrix becomes calcified chondrocytes within are starved for nutrients and die. Then osteoblasts lay down osteoid within the calcified matrix generating osseous tissue at the zone of ossification. The zone of ossification is the region of the epiphysial plate that's closest to the diaphysis. New osseous tissue is constantly being generated at the zone of ossification and replacing hyaline cartilage that's constantly being generated at the proliferative zone. In contrast to interstitial growth, oppositional growth leads to an increased thickness or a diameter of a long bone. The mechanism of oppositional growth involves osteoclasts resorbing bone from the inner surface while at the same time osteogenic cells in the periosteum generate osteoblasts that secrete osteoid forming new osseous tissue adjacent to the periosteum surrounding the long bone. Bone growth is regulated by hormones, the chemical messages that are secreted from endocrine glands. For example, growth hormone is secreted from the anterior pituitary gland and stimulates interstitial bone growth at the epiphyseal growth plate. During childhood growth hormone is regulating the rate at which our bones become longer and if there is excessive growth hormone signaling this can cause the bones to grow very quickly leading to a condition known as gigantism. In contrast if growth hormone signaling is abnormally low this could lead to a condition known as pituitary dwarfism where the long bones are shorter than normal. At the end of puberty the epiphyseal growth plate will mature into an epiphyseal line as all of the highland cartilage at the epiphyseal growth plate is replaced with compact bone. The maturation of the epiphyseal growth plate to form an epiphyseal line is stimulated by sex hormones estrogen and testosterone at the end of puberty. These hormones will slow the rate of chondrocyte division while stimulating an increase in osteoblast activity. This causes osseous tissue to be formed at a faster rate than the highland cartilage can grow and eventually all of the highland cartilage is replaced with osseous tissue forming an epiphyseal line from the epiphyseal growth plate. This ends the process of interstitial bone growth so your bones cannot become longer after the end of puberty and an abnormally elevated level of growth hormone later in life will not stimulate an increased interstitial bone growth however it could lead to acceleration of oppositional bone growth or acceleration of the growth of other tissues.