Skeletal System Levels of Organization
The skeletal system is organized into the following structural hierarchy, from microstructure to gross anatomy:
- Chemistry and molecular scale – Water, minerals, collagen, and other proteins.
- Nanoscale – Mineral crystals are embedded within collagen to form composite fibers.
- Submicron scale – Mineralized fibrils are organized into a lamella (plural is “lamellae”).
- Micron (micrometer) scale – Lamellae form osteons in compact bone or trabeculae in spongy bone.
- Macroscale – Compact and spongy bone combine together to form whole bones, and bones combine at articulations to form the skeletal system.
Bones constantly store and release calcium, phosphate, proteins, and other matrix components of bone. Within the matrix, the mineral crystals resist compression but are very brittle. The organic components, such as the collagen fibers and the cells, help give the bone some flexibility. The hierarchical organization of the skeletal system at different scales is important for its mechanical, biological, and chemical functions.
Molecules and Macromolecules
The major components of bone tissue at the molecular scale are minerals, water, collagen, and other proteins. At the next level of organization, small crystals of hydroxyapatite made of calcium and phosphate are embedded within collagen fibers to produce a composite (blended) material with high compressive and tensile strength.
The skeletal system protects and supports vital organs, allows our body to move, stores important minerals, and produces blood cells. There are several chemical elements and molecules required to maintain the many functions of the skeletal system. The chemical properties of these components support bone structure and function. On a chemical level, bone is divided into inorganic and organic (carbon-containing) components.
The primary inorganic components of bone are:
- calcium, which is required for many functions throughout the body;
- phosphorus (in the form of phosphate ions), which is a component of buffer systems and energy-rich molecules; and
- water, which contributes to the compressive resistance of bone and contributes to the fluid matrix of bone.
The primary organic components of bone are:
- collagen, the major structural protein (type I in bone and type II in cartilage); and
- proteoglycans, which are negatively charged glycosylated proteins (glycosylated means having carbohydrate sugar groups modifying the protein).
Bone is approximately 60 to 70 percent inorganic mineral and 10 percent water by weight. The remaining 20 to 30 percent of bone is organic matrix (osteoid), such as collagen and proteoglycans. Your body contains 1 to 2 kilograms of calcium and nearly 600 grams of phosphorous. Nearly 99 percent of the calcium and 86 percent of the phosphorous is stored in your bones.
Inorganic Components of Bone
Calcium ions (Ca2+) are stored in bone tissue, but can be released into the bloodstream when blood levels fall below optimal. Blood calcium is important for muscle contractions, nerve impulses, and blood clotting.
In bone, phosphorous (P) is found in the form of phosphate ions (H2PO4–). Outside of bone, phosphorous plays roles in energy storage (such as in ATP), and is required for the formation of DNA and RNA. Therefore, it is required for cellular growth, maintenance, and tissue repair.
When combined with hydrogen, phosphorous forms dihydrogen phosphate ions (H2PO4–). Dihydrogen phosphate acts as a buffer to maintain a constant pH balance by acting as either a hydrogen ion donor (acid) or a hydrogen ion acceptor (base). In all cells, a constant pH must be maintained to carry out cell functions.
As mentioned in previous sections, hydroxyapatite is an inorganic calcium phosphate mineral that is a primary component of bone. Crystal hydroxyapatite has the chemical formula: Ca10(PO4)6(OH)2.
During bone formation, the collagen fiber matrix is formed. Next, mineralization of the matrix occurs when calcium, phosphate, and water from the extracellular fluids combine to form insoluble hydroxyapatite. The hydroxyapatite incorporates into the small pores within collagen fibrils and crystallizes into long, thin, nanosized plates within the collagen network. The incorporation of hydroxyapatite within the collagen fibers contributes to the overall compressive strength of bone. Because the crystals are nanosized, they have a large surface area. The large surface area of the crystals makes it easy to release ions into the extracellular fluids when blood levels decrease.
Sometimes bones contain fluoride. Fluoride is similar to the hydroxyl ion in charge and size. When fluoride replaces the hydroxyl ion in hydroxyapatite crystals, it forms fluoroapatite. Fluoroapatite is a more compact and less soluble crystal than hydroxyapatite. Therefore, ion exchange at the crystal surface is slower. The primary role of fluoride in bone is to strengthen bone mineral.
Water is an important molecular component of bone matrix. Water is initially present in the spaces within the collagen matrix of the unmineralized bone extracellular matrix (osteoid). As crystals fill in the spaces between collagen fibrils, the bone is mineralized and the water is displaced. The water that remains in bone after this process is complete forms hydrogen bonds with polar, hydrophilic components of collagen. Water also assists with the compressive resistance of bone due to osmotic interactions caused by negatively charged proteoglycans.
In addition to calcium, phosphorous, water, and fluoride, the inorganic parts of bone also contain sodium, potassium, carbonate, and magnesium. Although these molecules do not form their own crystals, they are bound to hydroxyapatite crystals within bone mineral.
Organic Components of Bone
You can think of the hydroxyapatite in bones as being similar to concrete. The chemical structure of hydroxyapatite gives it a high mechanical strength under compression (squeezing force), but little strength under tension (pulling force). If our bones were made only of hydroxyapatite, they would be very fragile, like concrete. They would break easily under tension. The organic components of bone help to give it additional strength and flexibility.
Collagen, a ropelike, fibrous protein, is the major organic component of bone. Like rope, collagen has significant mechanical strength under tension. Therefore, collagen provides tensile strength to the bones. The spiral arrangement of collagen in combination with its ECM (extracellular matrix) components, such as water and specialized proteins, also makes bone more elastic and less brittle, so that it can absorb shock more easily.
Bone matrix is a network of collagen fibers and hydroxyapatite. It is strong under both tension and compression. Furthermore, the collagen contributes to its ability to absorb sudden forces without breaking.
Collagens are a class of fibrous proteins found in bone, cartilage, and other connective tissues. The primary structure of collagen has repeats of glycine-proline-X, where X can be any other amino acid. This repeated arrangement gives collagen a unique helical secondary structure. The tertiary structure of collagen is a triple helix fibril, which further twists into a quaternary structure of a collagen fiber. The resulting “twisted, twisted, twist” is similar to the higher-ordered structures in rope.
Type I collagen is the primary form of collagen found in bone. The collagen fibers in bone are approximately 300 nanometers long, and are arranged in a staggered pattern. During bone formation, the collagen fiber matrix is deposited first. Proteoglycans are a second class of organic components found in bone. Proteoglycans are macromolecules composed of proteins with negatively charged glycosylated modifications. There are a number of proteoglycans, which are classified by the type of side chains on the core protein. The side chains on the proteoglycans are linear carbohydrates. As with cartilage, the presence of the negatively charged proteoglycans contributes to the resilience of the tissue and retention of water within the matrix. Proteoglycans also bind and release molecules for cell signaling.
Organic and Inorganic Combination
Mineralization of the bone matrix occurs when calcium, phosphate, and water from the extracellular fluids combine to form insoluble hydroxyapatite. The hydroxyapatite incorporates into the small pores within collagen fibrils and crystallizes into long, thin, nanosized plates within the collagen network. The incorporation of hydroxyapatite within the collagen fibers contributes to the overall compressive strength of bone. Within the bone matrix, the minerals, water, collagens, and proteoglycans function together to provide strength in tension and compression. Additionally, this unique environment binds and releases chemicals into the extracellular fluids for use throughout the body.
Osteogenesis imperfecta (from osteo–, meaning bone, and genesis, meaning production or beginning) is a congenital (genetic) disorder that affects the structure and strength of bones. The condition is primarily caused by genetic mutations that affect the structure and/or quantity of type I collagen produced by the body. Remember that collagen is an important component of the extracellular matrix of bone tissue. In people with osteogenesis imperfecta, the lack of collagen (or presence of defective collagen) prevents the extracellular matrix from forming correctly. The mineral structure of the bone is weakened, and as a result, the bones are unusually brittle.
The bones of people with osteogenesis imperfecta break extremely easily, sometimes with only small amounts of pressure. The bones’ brittleness reduces their ability to support and protect the body. They also typically take longer to heal and may be more prone to infection.
Bones become stronger and thicker when they are exposed to regular stress. Conversely, bones that do not experience regular stress may lose extracellular matrix and become less dense. In a person with osteogenesis imperfecta, bones that break often (and therefore spend a lot of time immobilized in casts or restraints) are exposed to much less stress. As a result, they may lose even more extracellular matrix and become even more brittle.
Extracellular Matrix in Bone
You have already learned about the hydroxyapatite and collagen combination, which is responsible for giving bones their rigidity. The skeletal system is an excellent example of a system that is primarily composed of extracellular matrix. Generally, cells of the body function within a matrix to hold them together. In the case of bone, the extracellular matrix (ECM) is composed of crystals of hydroxyapatite and long collagen proteins. The hydroxyapatite and collagen work together to give bone its unique properties of strength, compressive resistance, and flexibility.
Cells in Bone
The previous section described the importance of the bone matrix components calcium and hydroxyapatite in maintaining bone rigidity. However, bone remodeling is equally important to maintaining bone health. Throughout your lifetime, your bones are constantly remodeled and repaired. There are three main cell types in bone, which maintain bone balance and strength:
- osteoclasts, which break down and reabsorb bone;
- osteoblasts, which deposit and build new bone; and
- osteocytes, which are mature bone cells that act as sensors for repair.
Think of the bones of your body as a rapidly expanding city. When the old buildings get outdated, they are either remodeled to make enhancements or knocked down to make room for the new ones. As soon as a building is knocked down, a new one is erected in its place. The construction crew recycles the old building materials. Many city planners constantly monitor the building progress and talk with one another about which sections of the city will get the available resources.
Osteoclasts secrete an acid that dissolves the inorganic components of bone: calcium and phosphate. Osteoclasts also contain enzymes that digest the organic components of the bone matrix, such as the proteins and proteoglycans. Bone resorption (osteolysis) is complete when small cavities remain on the bone surface. Osteoclast activity is important for creating the medullary cavities of diaphyses, which house bone marrow. (Remember that the diaphysis is the main shaft of a long bone.) Osteoclasts are important for removing calcium from bones if the blood calcium levels fall, such as when a diet is deficient in calcium. Remember calcium is critical for life and if levels fall, it could be fatal if it wasn’t taken from the bones.
Osteoblasts build bone and fill in the cavities created by osteoclasts. Osteoblast cells secrete osteoid (the organic portion of the bone matrix) around them, and then mineralize the matrix to generate rigid bone tissue. Bone mineralization occurs through osteoblast secretion of an enzyme called alkaline phosphatase. Alkaline phosphatase cleaves phosphate groups to provide the necessary phosphate for building hydroxyapatite. Osteoblasts are stimulated when blood calcium levels increase. The excess calcium is deposited into the bones for storage.
After bone mineralization, osteoblasts trapped within the matrix differentiate into osteocytes. Osteocytes have long processes (outgrowths or protrusions) for connection to other osteocytes within the bone. This arrangement allows osteocytes to act as mechanical sensors. Osteocytes sense mechanical strain within bone and regulate the activity of osteoblasts or osteoclasts, depending on needs for calcium and phosphate. To maintain bone strength, bone resorption and bone deposition must be in constant balance with each other.