Osteoclast

Osteoclasts are one of three main types of cells in bone: osteoclasts, osteoblasts, and osteocytes. Osteoclasts remove bone and work in conjunction with osteoblasts, which build bone. The bone resorption performed by osteoclasts is important because it allows the body to keep existing bones strong and build new bone when necessary. Osteoclasts play a key role in how infants and children grow and how bones heal after a fracture. They also contribute to the health of a person's skeleton during aging.

Background

The word osteoclast comes from the Greek words osteon, which means bone, and klastos, which means broken. Osteoclasts were identified and named in 1873 by Swiss anatomist Rudolf Albert von Kölliker (1817–1905). Osteoclasts are multinucleated cells, or cells with more than one nucleus. The nucleus contains the genetic material that defines the cell's function and purpose. Osteoclasts generally have about five to twenty nuclei.

Osteoclasts are formed from hematopoietic precursor cells of the monocyte–macrophage lineage in the bone marrow, known as osteoclast precursors (OCPs), sometimes called preosteoclasts, and may circulate in the blood before settling in bone tissue. Eventually, they settle in small ridges or indentations in the bone known as Howship's lacunae. Osteoclasts are directed to these places by the release of the parathyroid hormone (PTH), which prompts the bone-building osteoblasts to release RANKL (receptor activator of nuclear factor-kappa B ligand). RANKL attracts osteoclasts to bone areas that need to be broken down to form new bone.

Once they attach firmly to the bone, osteoclasts create a protective compartment around the area. The part of this compartment directly attached to the bone becomes the ruffled membrane, which releases hydrogen ions and enzymes that begin dissolving the bone. As the bone is broken down, the minerals contained in the bone are dissolved, and enzymes are generated that dissolve the collagen and other components of the bone. Osteoclasts are pre-programmed to self-destruct when their work is complete, so when the bone in the protective compartment has been completely removed, the osteoclast dies.

In most circumstances, once the osteoclast has completed its work, the osteoblasts rebuild the area with fresh bone; this is known as bone remodeling. However, in some cases, this process may be out of balance due to illnesses, such as cancer, and dietary deficiencies. Some medications also alter the bone remodeling process. Age can also interfere with the effectiveness of the bone remodeling process. Children and younger people can generally regenerate bone faster than older people. Osteoporosis is the most common result of age-related bone remodeling problems.

Advancements in computational biology have enhanced osteoclast image analysis, facilitating more accurate assessments of osteoclast activity and informing osteoporosis research. ​Studying osteoclasts using single-cell analyses, scientists discovered that these cells are not as uniform as once believed. Called osteoclast heterogeneity, several types of osteoclasts exist that have specialized functions in bone metastasis, different origins, and differing lifespans. Osteoclasts have been implicated in bone formation, immune regulation, and hematopoiesis. The study of how the immune system and the skeleton affect each other is called osteoimmunology, and it helps explain bone loss in conditions such as rheumatoid arthritis and other inflammatory diseases.

Role in Childhood

Developing fetuses and newborn babies have skeletons with about three hundred parts, unlike the 206 a child will have as an adult. These parts are soft and mainly made of cartilage, a firm but very flexible form of connective tissue found in the body. This cartilage gradually turns into bone through a process known as ossification. Children also undergo rapid growth in their earliest years, and the newly formed bone is frequently remodeled to grow longer, thicker, and stronger so the skeleton can support the developing child. Osteoclasts play a key role in breaking down bone so it can be rebuilt into larger sizes. The bone formation process related to growth will continue until the person reaches the late teens or early twenties, when the bones have reached maximum size.

Role in Fracture Healing

Osteoclasts work efficiently with osteoblasts to help fix fractured bones during childhood. Osteoblasts and osteoclasts continuously work at a fast pace during childhood, so the systems needed to create new bone are already very active at the time of a fracture. This means that it takes less time for the body to begin healing a fracture in a child than it does in an adult, where the system is called upon less often and needs to reactivate to remodel the broken bone.

Osteoclasts are part of the final segment of the healing process for a fractured bone. The broken parts are held together temporarily by collagen-rich soft tissue before being replaced by new bone generated by osteoblasts. This process leaves a thickened, larger bump around the break. Osteoclasts will slowly dissolve this extra bone to restore the bone to its original shape as closely as possible.

Role in Aging

Sometimes, the balance between how quickly osteoclasts remove old bone and how quickly osteoblasts replace it is out of balance. This is a relatively common occurrence in older people, particularly women who have gone through menopause, which is the cessation of the monthly egg-releasing cycle of the reproductive system. The change in the reproductive process alters the amount of the hormone estrogen in the body, and estrogen is part of the process that regulates the number of osteoblasts and osteoclasts the body produces. When more osteoclasts are produced than osteoblasts, bone is removed faster than it can be replaced. This results in bones with holes and tunnels instead of being solid, decreasing bone strength and increasing the likelihood of a break. This condition is known as osteoporosis.

In addition, because osteoclasts function to maintain bone health throughout life, they tend to be attracted to aging bone. When the body can produce enough osteoblasts to rebuild the bone absorbed and removed by the osteoclasts, this tendency of the osteoclasts does not present a problem. However, this balance can be altered by diet, other health problems, and some medications. Because older people tend to have more health problems and generally take more medication, they have an increased likelihood of their osteoclasts dissolving bone faster than osteoblasts can replace it, putting them at a greater risk of developing osteoporosis.

Bibliography

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