New deposition and resorption of bone
Osteoblasts are found on the outer surface of bones and in bone cavities. Bone is continually destroyed by the presence of osteoclasts, which are large, phagocytic, multinucleated cells that are derivatives of monocytes or monocyte-like cells that form in bone marrow.
Bone deposition by osteoblasts
Bone is continuously deposited by osteoblasts, as well as continuously reabsorbed where osteoclasts are active.
Figure. The activity of osteoclasts and osteoblasts in the same bone.
Osteoblasts are found on the outer surface of bones and in bone cavities. A small amount of osteoblastic activity occurs continuously in all living bones (about 4 percent of all surfaces at any given time in adults, so new bone is constantly forming). Fort.
Bone destruction - the function of osteoclasts
Bone is continuously destroyed by the presence of osteoclasts, which are large, phagocytic, multinucleated cells (containing about 50 nuclei) that are derivatives of monocytes or cells like monocytes form in the bone marrow. Active osteoclasts make up less than 1 percent of the bone surface of an adult.
Histologically, bone destruction occurs immediately in addition to osteoclasts. The mechanism of this destruction is thought to be as follows: The osteoclast sends the hair-like parts towards the bone, forming a rough surface. The villi secrete two types of substances: (1) proteolytic enzymes, released from the lysosomes of osteoclasts, and (2) several acids, including citric and lactic acids, released from mitochondria and secret bags. These enzymes digest or break down the underlying structures of bone and are responsible for the release of bone salts. The osteoclasts also absorb minute particles of bone matrix and crystals by phagocytosis, then break down and release the products into the bloodstream.
Figure. Bone resorption by osteoclasts. Parathyroid hormone (PTH) binds to receptors on osteoblasts, causing them to form receptor activators for nuclear factor -B ligand (RANKL) and release macrophage-stimulating factor. cells (M-CSF). RANKL binds to RANK and M-CSF binds to its receptors on progenitor cells, causing them to differentiate into mature osteoblasts. PTH also reduces the production of osteoprotegerin (OPG), which inhibits the differentiation of preosteoclasts into mature osteoclasts by binding to RANKL and preventing it from interacting with its receptor on preosteoclasts. Mature osteoblasts develop a ruffled border and release enzymes from lysosomes, as well as acids that promote bone resorption. Osteocytes are osteoblasts that have been encased in the bone matrix during the production of bone tissue; Osteocytes form an interconnected system of cells that spread all over the bone.
As mentioned before, the hormone PTH stimulates osteoclast activity and bone resorption, but this process occurs through an indirect mechanism. The osteoclasts involved have no receptors for the hormone PTH.
Instead, osteoclasts signal to osteoclast progenitors to produce mature osteoclasts. The two osteoblast proteins responsible for this signalling are the receptor activator for nuclear factor κ-B ligand (RANKL) and macrophage colony stimulating factor, both of which are required. for the formation of mature osteoclasts.
PTH binds to receptors on the side of osteoblasts, stimulating the synthesis of RANKL, or osteoprotegerin ligand (OPGL). RANKL binds to its receptor (RANK) on osteoclast progenitor cells, causing them to differentiate into mature multinucleated osteoclasts. Mature osteoclasts then develop a rough surface and release enzymes and acids that promote bone resorption.
Osteoblasts also produce osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, a cytokine that inhibits bone resorption. OPG acts as a "bait", binding to RANKL and preventing interaction with its receptor, which prevents the differentiation of osteoclast progenitors into mature osteoclasts involved in the process. bone resorption.
OPG antagonizes the destructive activities of PTH, in mice lacking the OPG fusion gene, there was a marked reduction in bone mass compared with mice with normal OPG gene.
Although the factors that regulate OPG are poorly understood, vitamins D and PTH appear to stimulate the production of mature osteoclasts through a dual action of both inhibiting OPG production and stimulating RANKL synthesis. Glucocorticoids also promote osteoclast activity and bone resorption by increasing RANKL production and decreasing OPG formation. On the other hand, the hormone estrogen stimulates the production of OPG. The balance of OPG and RANKL produced by osteoblasts plays an important role in determining osteoclast activity and bone resorption.
The importance of therapeutic approaches to the OPG-RANKL system is still being tested. Several new drugs that mimic the effects of OPG by blocking the interaction of RANKL with its receptor appear to be useful for the treatment of osteoporosis in postmenopausal women and in some patients with bone cancer. .
Balancing bone deposition and destruction
Except for growing bone, the ratio between deposition and destruction is usually equal, so the total mass of the bone remains constant. The osteoclasts are usually small in number, but they are concentrated together and once the number of osteoclasts begins to grow. They usually take 3 weeks to destroy the bone, creating a tunnel 0.2-1 mm in diameter and several millimetres long. At the end of the process, the osteoclasts disappear, and osteoclasts enter these tunnels to help new bone begin to grow. The bone deposition continued for several months, with the new bone being paved in successive layers of slices in concentric circles (lamellae) on the inner surface of the cavity until the tunnel closed. The deposition ceases when the bone begins to invade the blood vessels responsible for the regional blood supply. The channels in which blood vessels run are called Haversian channels is the remains of the original cavity. Each new area of bone deposited in this way is called an osteon.
The value of constantly renewing bones
The continuous deposition and destruction of bone hold several important physiological functions. First, bone can adjust its strength in proportion to bone stress. As a result, bones thicken when subjected to heavy loads. Second, even the shape of the bone can be rearranged to better accommodate mechanical forces through deposition and bone destruction to match the direction of the load. Third, because old bone becomes relatively brittle and fragile, new substrates are needed to replace the degenerated substrates. Therefore, the flexibility of the bone is always maintained. Indeed, in children's bones, the rate of deposition and destruction is very rapid, so children's bones are less brittle than in the elderly with slow deposition and destruction rates.
Bone strength (Bone “Stress.”) controls the rate of bone deposition
The bone is deposited in such a way that it corresponds to the pressure to which the bone is subjected. For example, the bones of athletes are heavier than those of others. In addition, if a person has 1 leg in a cast but continues to walk on the opposite leg, the bone in the leg becomes thin and loses about 30% calcium within a few weeks, while the contralateral bone remains thick and normal calcium density. Thus, persistent physical stress stimulates bone deposition and calcification.
The load level also contributes to the shape of the bone in some cases. For example, if a long bone such as a leg bone breaks centrally and then recovers at the junction, the inward compression of the corners increases bone deposition. Increased destruction occurs on the outside at the corners where the bone is not compressed. Therefore, after many years of increased deposition on the inside of the flexor bone and destruction on the outside, the bone can become nearly straight, especially in children because of the rapid renewal of bone at a young age. .
Figure. Bone structure
The repair of broken bones by osteoblasts
Fractures maximally activate all osteoblasts in the periosteum and in the bone that participate in the healing of the fracture. In addition, large numbers of new osteoblasts are formed almost immediately from "osteoprogenitor" cells, which are bone stem cells in the outer surface of the bone, called the "periosteum". Then, within a short time, a large bulge includes osteoblastic tissue and new bony basal fractures. After a short time, the deposition of calcium salts develops between the broken ends of the bone. This area is called the “callus”.
Many orthopaedic surgeons use bone compression to accelerate fracture healing. This acceleration is accomplished using special mechanical devices that hold the broken ends together so that the patient can continue using the bones immediately. This practice puts pressure on the opposite end of the broken bone, which increases the activity of the osteoblasts at the fracture and often shortens the healing time.