The main structure of the skeletal system is composed ofcartilage and bone. Both are connective tissues, that is, they are made ofcells which are embedded in the matrix with intracellular fibres. They form theessential structural component of the body.
Cartilage and bone are different intheir composition and function. Cartilage is a semi-rigid connective tissuetherefore it does not contain the hard properties of bone, it is very flexible.The mature cartilage is avascular meaning it contains no blood vessels, thismakes healing process difficult and long.
Nutrients required for the cartilageare diffused through the matrix. Due to its flexibility, cartilage supportssoft tissue such as the airway of the respiratory system or the auricle of theear. It has also been identified in the meniscus of the knee, the nose andpubic bone. Bone is the most rigid of the connective tissue, its extracellularmatrix is rigid. It is strengthened through the process of calcification,minerals which have been deposited in the matrix, and is the main store andsource of calcium phosphate. The function of bone includes supporting the bodyby aiding in movement and hemopoiesis.
Dysfunction of bone and cartilage canconsequently lead to Osteoarthritis and Osteomalacia. The initial formation of cartilage requires the condensationof chondroblasts into chondrocytes. Chondroblasts are mesenchymal progenitorcells which are important in chondrogenesis due to their ability todifferentiate into chondrocytes and form extracellular matrix which togetherwill form the cartilage. They also produce extracellular matrix components suchas proteoglycan and collagen fibres. Chondrocytes are the mature cartilagecells, they are embedded in the cartilage matrix and trapped in a structurecalled the lacunae, and the number of chondrocytes in lacunae determines howflexible the cartilage is. The role of chondrocytes is for the production andmaintenance of the cartilage matrix. There are three types of cartilage, this includes elasticcartilage, hyaline cartilage and fibrocartilage. Elasticcartilage contains threadlike structures which makes up the elastic fibresinside the extracellular matrix.
Associated with the elastic fibres arechondrocytes which are in lacunae. Perichondrium surrounds the surface of thecartilage, it contains blood vessels and nerves which is essential for thedevelopment of new cartilage. Elastic cartilage is located on areas such as thetrachea, true vocal cords, and ligaments of the penis and lung tissue. Theirfunction is to allow the stretching of some organs such as those of the lungswhich recoils when exhaling. It ensures that after being stretched, they recoilto their original shape (Tortora, 2011).
Hyaline cartilage contains fine collagenfibres which are not visible when using ordinary staining technique. They alsocontain chondrocytes in lacunae with their surface surrounded by periosteum.Hyaline cartilage has a resilient gel as ground substance and are blue-whiteshiny substance in the body. It is mainly located at the end of long bones,fetal skeleton and part of the larynx. They enable smooth movement of jointspreventing them from grinding together. These are the most common type ofcartilage in the body however, they are also the weakest. Hyaline cartilage injoints are referred to as articular cartilage (Tortora, 2011). The structureof fibrocartilage consists of thick visible collagen fibres in ground substance within the extracellularmatrix.
They also contain chondrocytes in lacunae however, they do not haveperiosteum. They are in intervertebral discs and pubic symphysis. Their roleinvolves supporting and joining different structures together. These are thestrongest of the cartilage because they contain less chondrocyte therefore aremore rigid (Tortora, 2011).
The growth of cartilage involves either interstitial growthor appositional growth. Interstitial growth occurs within the tissue by theincrease in size because of the division of chondrocytes and increaseproduction of extracellular matrix from inside the lacunae. The increase amountof the matrix further separates the chondrocytes from each other, expanding thecartilage from within. Division of chondrocytes is by mitosis, producing twochondrocytes per lacunae. This increases the cartilage in width.
Appositionalgrowth occurs along the outside edge of the cartilage. There are stem cells inthe perichondrium which undergoes mitosis to produce chondroblasts, these areadded to the periphery producing matrix and differentiating into chondrocyteswhich forms new lacunae. The lacunae areadded to an existing matrix leading to the formation of a larger piece ofcartilage. Appositional growth increases the cartilage in length and s used forendochondral bone formation.Adult human has a total of 213 bones in their body (Clarke, 2008).These bones undergo modelling for replacement of old or damaged bone. Bones areseparated into four categories which are long bones, short bones, flat bonesand irregular bones.Longbones include the femur and clavicles, they are a result of endochondral andmembranous bone formation.
Long bones are made of the diaphysis, epiphysis andmetaphysis. The epiphysis is the ending of bone, it forms a rounded region atthe end and strengthens the joints. It also acts as an attachment site for tendonsand ligaments. Where the long bone may meet another contains a thin layer ofarticular cartilage, reducing friction. The metaphysis is between the epiphysisand diaphysis, it contains epiphyseal which is a growth plate that allows thebones to grow longer. It is made from hyaline cartilage.
The diaphysis is madefrom mainly compact bone whereas epiphysis and metaphysis are made of spongybone (Clarke, 2008).On the outside of the bone is dense irregular connectivetissue, periosteum. They contain two layer, the inner cellular and vascularlayer allows for the formation of new bone whereas the outer fibrous layer aidsin insertion of ligaments, tendons and muscles (Buckwalter and Cooper, 1987). It acts as an anchor for bloodvessels and nerves and is held firmly to the bones by perforating fibres embeddedin the bone matrix. Stem cells are found in the periosteum, they migrateallowing the growth of bone and healing properties. The spongy bone containsthe periosteum but not endosteum. Endosteum lines the inside of the bone marrowcavity, however small cavities on the spongy bone is lined with endosteum. Thebone matrix consists of organic components such as bone cells, collagen fibresand ground substances.
Also, inorganic substances such as bone salt crystals,hydroxyapatite, which hardens the ground substance and calcium phosphate andhydroxide. There are two types of bone tissue, compact bone and spongybone. Flat bones contains both spongy and compact bones, they are found at theskull.Thecompact bone makes the exterior of the flat bone and the shaft of the longbone.
Compact bone and spongy bone consists of osteons, also known as theHaversian system, they are cylindrical and form branched network within thecortical bone. Compact bone consists of an outer periosteal surface, which isessential for appositional growth and repair. It also consists of an innerendosteal surface. The spongy bone alsocontains osteons called packets. They are semilunar and made of concentriclamellae (Clarke, 2008). The bone has four different types of cell, these areosteoprogenitor cells, osteoblasts, osteocytes and osteoclast. Osteoproginitorcells are stem cells which are located at the periosteum and endosteum, therole is to produce more stem cells or osteoblasts. Osteoblast are located at the surface of the bone, they arerequired for the formation of bone.
Osteoblast is characterized by the presenceof protein synthesising cell which includes rough endoplasmic reticulum and theGolgi apparatus. They produce the unmineralized organic component of bone(osteoid) toward the matrix of the bone. Osteoblast are derived from mesenchymalstem cells, this process requires the expression of specific genes. Thisincludes the pathway of bone morphological protein (BMPs) and members of thewingless (Wnt). Osteoblast differentiation is regulated by expression ofRunt-related transcriptional factors 2, Distal-less homeobox 5 and osterix(osx).
Osteoblast progenitor shows alkaline phosphate activity, this makespre-osteoblast which are differentiated to osteoblast by the increaseexpression of osx and formation of bone matrix proteins, collagen I andosteocalcin (Florencio-Silva et al., 2015).Osteocytes are derived from osteoblasts, they are located inlacunae which are surrounded by mineralized bone matrix. Osteocytes in spongybone are round whereas in compact bone are more elongated. They are requiredfor the maintenance of the strength of bones. Osteocytes derived osteoblastinvolves protein E11/gp38. It is shown to be highly expressed in embeddedosteocytes Osteoclast is a multinucleated bone cell, its functioninvolves absorbing bone tissue during growth and repair.
They are made fromhematopoietic stem cell which are stimulated by macrophage colony-stimulatingfactor and RANK ligand. These two factors are responsible for gene expressionin osteoclast. The binding of M-CSF and RANKL to its receptor in osteoclastprecursor stimulates its proliferation, also inhibiting apoptosis (Florencio-Silva et al., 2015).Bone formation: intramembranous ossification and endrochondralossification.
Intramembranous ossification involves the differentiation andcondensation of mesenchymal stem cell into compact nodule. Numerous cellsundergo changes to become osteoblast which then secretes acollagen-proteoglycan matrix containing calcified salt. As a result, the pre-boneis calcified.
Osteoblasts are trapped in the calcified matric, becomingosteocytes. Continuous calcification leads to the removal of bony spicules awayfrom the initial ossification site. Calcified spicules are surrounded bycompact mesenchymal cells (MS) forming the periosteum. The process ofintramembranous ossification requires bone morphogenetic protein (BMPs) andactivation of transcription factor (CBFA1). BMPs sends instructions for MS tobecome bone, it activates the Cbfa1 gene in the cells which transforms MS intoosteoblast (Gilbert, 2000).
Endrochondral ossification involves the formation ofcartilage from mesenchymal stem cells, the cartilage is then used as a templatefor bone formation. This process is divided into five stages. The first stageinvolves the formation of the cartilage from the MSC, this is initiated byparacrine factors which causes nearby mesodermal cells to expresstranscriptional factors Pax1 and Scleraxis. These transcription factorsactivate cartilage specific genes. The second stage involves the condensationinto compact nodules and later differentiation into chondrocytes which is thecartilage cell.
The initiation of condensation is performed by N-cadherin andthe maintenance of it requires N-CAM in mouse embryo, however SOX9 gene isexpressed in humans. In the third stage, proliferation of the chondrocytesoccurs for formation of model required for bone. When the chondrocytes divide,they secrete extracellular matrix. Inthe fourth stage, the chondrocyte stop dividing and increase their volumebecoming hypertrophic. This allows mineralization of the matrix by calciumcarbonate. The fifth stage is the invasion of cartilage model by blood vesselsallowing the death of chondrocyte cells by apoptosis. The space left becomesbone marrow and the death of cartilage cells lead to the formation ofosteoblast which forms the bone matrix until all the cartilage has beenreplaced by bone.
However, not all cartilage are calcified, there is acartilaginous area at the ends of long bone called epiphyseal growth plates whichcontains “a region of chondrocyte proliferation, a region of maturechondrocytes, and a region of hypertrophic chondrocyte” (Gilbert, 2000). Osteomalacia is a metabolic disease from limitedmineralization of osteoid in mature compact and spongy bone. It involves theinhibition of mineral calcification and deposition, therefore there is nochange in bone mass, and replaced bone consists of soft osteoid rather than arigid born. This is a result of vitamin D deficiency which decreases plasmacalcium concentration, leading to the activation of PTH which stimulates renalclearance of phosphate.
The decrease in phosphate in the bone inhibitsmineralization. In contrast, osteoarthritis is an age-related disorderassociated with the loss and damage of the articular cartilage, it is usuallylocated in the hips or hands. The exact cause still remains unclear however ithas been suggested that genetics, inflammation and metabolic factors play animportant role. It involves a complexinteraction of transcriptional factors, cytokines and growth factors.
Clinicalmanifestation includes pain in the joints, stiffness, discolouration, musclewasting and deformity. In Osteomalacia, the individual may experience muscularand skeletal pain, they are also more common in the hips. Muscular weakness maylead to “a waddling gait”, facial deformities may be present and the bone ofthe back can easily fracture with little effort (Huether and McCance, 2012).
The general principles of some treatment for Osteomalaciaare taking vitamin D supplements, bisphosphate, and chelation of bone aluminiumand adjustment of serum calcium and phosphorus level. For osteoarthritis, thepatient are examined using radiologic studies and clinical assessment, they areencouraged to rest and use of crutches to prevent joint contraction. Injectionwith hyaluronic acid reduces knee pain, however new investigation are made toif agents such as leptin would work. Surgery can be used to place artificialimplants. In conclusion, bone and cartilage are essentialfor the development of the skeletal system, dysfunction with either of them maylead to disorders such as Osteomalacia or osteoarthritis which can be lifechanging.