Bone Development PDF

Bone development  OBJECTIVES a. Intramembranous ossification. b. Endochondral ossification.  Osteogenesis Bone development or osteogenesis occurs by one of two processes: 1.Intramembranous ossification, in which osteoblast...

Bone development  OBJECTIVES a. Intramembranous ossification. b. Endochondral ossification.  Osteogenesis Bone development or osteogenesis occurs by one of two processes: 1.Intramembranous ossification, in which osteoblasts differentiate directly from mesenchyme and begin secreting osteoid. 2. Endochondral ossification, in which a preexisting matrix of hyaline cartilage is eroded and invaded by osteoblasts, which then begin osteoid production.  in both processes woven bone is produced first and is soon replaced by stronger lamellar bone. During growth of all bones, üareas of woven bone üareas of bone resorption üareas of lamellar bone all exist contiguous to one another.  Intramembranous Ossification Intramembranous ossification, by which most flat bones begin to form, takes place within condensed sheets (“membranes”) of embryonic mesenchymal tissue. Most bones of the : üskull and jaws üThe scapula and clavicle are formed embryonically by intramembranous ossification.  Within the condensed mesenchyme bone formation begins in ossification centers, areas in which osteoprogenitor cells arise, proliferate, and form incomplete layers of osteoblasts around a network of developing capillaries. Osteoid secreted by the osteoblasts calcifies, forming small irregular areas of woven bone with osteocytes in lacunae and canaliculi.  Continued matrix secretion and calcification enlarges these areas and leads to the fusion of neighboring ossification centers. The anatomical bone forms gradually as woven bone matrix is replaced by compact bone that encloses a region of cancellous bone with marrow and larger blood vessels. Mesenchymal regions that do not undergo ossification give rise to the endosteum and the periosteum of the new bone.  In cranial flat bones, lamellar bone formation predominates over bone resorption at both the internal and external surfaces. Internal and external plates of compact bone arise, while the central portion (diploë) maintains its cancellous nature. The fontanelles or “soft spots” on the heads of newborn infants are areas of the skull in which the membranous tissue is not yet ossified.  Endochondral Ossification Endochondral ossification takes place within hyaline cartilage shaped as a small version, or model, of the bone to be formed. This type of ossification forms most bones of the body and is especially well studied in developing long bones, where it consists of the sequence of events. üIn this process ossification first occurs within a bone collar produced by osteoblasts that differentiate within the perichondrium (transitioning to periosteum) around the cartilage model diaphysis.  The collar impedes diffusion of oxygen and nutrients into the underlying cartilage, causing local chondrocytes to swell up (hypertrophy), compress the surrounding matrix, and initiate its calcification by releasing osteocalcin and alkaline phosphatase. The hypertrophic chondrocytes eventually die, creating empty spaces within the calcified matrix.  One or more blood vessels from the perichondrium (now the periosteum) penetrate the bone collar, bringing osteoprogenitor cells to the porous central region. Along with the vasculature newly formed osteoblasts move into all available spaces and produce woven bone. The remnants of calcified cartilage at this stage are basophilic and the new bone is more acidophilic.  This process in the diaphysis forms the primary ossification center, beginning in many embryonic bones as early as the first trimester. Secondary ossification centers appear later at the epiphyses of the cartilage model and develop in a similar manner. During their expansion and remodeling both the primary and secondary ossification centers produce cavities that are gradually filled with bone marrow and trabeculae of cancellous bone.  With the primary and secondary ossification centers, two regions of cartilage remain: Articular cartilage within the joints between long bones, which normally persists through adult life The specially organized epiphyseal cartilage (also called the epiphyseal plate or growth plate), which connects each epiphysis to the diaphysis and allows longitudinal bone growth.  The epiphyseal cartilage is responsible for the growth in length of the bone and disappears upon completion of bone development at adulthood. Elimination of these epiphyseal plates (“epiphyseal closure”) occurs at various times with different bones and by about age 20 is complete in all bones, making further growth in bone length no longer possible. In forensics or through x-ray examination of the growing skeleton, it is possible to determine the “bone age” of a young person, by noting which epiphyses have completed closure.  An epiphyseal growth plate shows distinct regions of cellular activity and is often discussed in terms of overlapping but histologically distinct zones , starting with the cartilage farthest from the ossification center in the diaphysis: 1. The zone of reserve (or resting) cartilage is composed of typical hyaline cartilage. 2. In the proliferative zone, the cartilage cells divide repeatedly, enlarge and secrete more type II collagen and proteoglycans, and become organized into columns parallel to the long axis of the bone. 3. The zone of hypertrophy contains swollen, terminally differentiated chondrocytes compress the matrix into aligned spicules and stiffen it by secretion of type X collagen. Unique to the hypertrophic chondrocytes in developing (or fractured) bone, type X collagen limits diffusion in the matrix and with growth factors promotes vascularization from the adjacent primary ossification center. 4. In the zone of calcified cartilage, chondrocytes about to undergo apoptosis release matrix vesicles and osteocalcin to begin matrix calcification by the formation of hydroxyapatite crystals. 5. In the zone of ossification bone tissue first appears. Capillaries and osteoprogenitor cells invade the now vacant chondrocytic lacunae, many of which merge to form the initial marrow cavity. Osteoblasts settle in a layer over the spicules of calcified cartilage matrix and secrete osteoid which becomes woven bone. This woven bone is then remodeled as lamellar bone. Notes Ølongitudinal growth of a bone occurs by cell proliferation in the epiphyseal plate cartilage. ØAt the same time, chondrocytes in the diaphysis side of the plate undergo hypertrophy, their matrix becomes calcified, and the cells die. ØOsteoblasts lay down a layer of new bone on the calcified cartilage matrix. Because the rates of these two opposing events (proliferation and destruction) are approximately equal, Øthe epiphyseal plate does not change thickness, but is instead displaced away from the center of the diaphysis as the length of the bone increases. ØGrowth in the circumference of long bones does not involve endochondral ossification but occurs through the activity of osteoblasts developing from osteoprogenitor cells in the periosteum by a process of appositional growth which begins with formation of the bone collar on the cartilaginous diaphysis. ØT h e i n c r e a s i n g b o n e c i r c u m f e r e n c e i s accompanied by enlargement of the central marrow cavity by the activity of osteoclasts in the endosteum.