Bone And Cartilage Flashcards
(28 cards)
Cartilage cells
The cells of cartilage are chondroblasts and chondrocytes. Chondroblasts are actively dividing cells, often flattened and irregular in shape, and are abundant in growing tissue where they synthesize the extracellular matrix. As chondroblasts mature and lose the ability to divide, they develop into the larger but metabolically less
active chondrocytes. Chonrocytes synthesize and secrete all of the major components
of the cartilage matrix.
Hyaline cartilage
Hyaline (glassy) cartilage has a homogeneous, opalescent appearance, sometimes appearing bluish. It is firm and smooth to the touch and shows considerable deformability. The size, shape and arrangement of cells vary at different sites with age. Chondrocytes are flat near the surface perichondrium. Groups of two or more cells frequently form a cell nest (isogenous cell group) surrounded by a basket of fine collagen fibrils. Within such a chondron, daughter cells of a common chondroblast often meet at a straight line.
Fibrocartilage
Fibrocartilage is a dense, whitish tissue with a distinct fibrous texture. It forms a versatile antough material that combines considerable tensile strength with the ability to resist high compressive forces and to distribute them evenly on to underlying bone.
The articular surfaces of bones that ossify in mesenchymal membranes (e.g. squamous temporal, mandible and clavicle) are covered by white fibrocartilage.
A transitional zone of irregular bundles of coarse collagen and active fibroblasts separates the superficial and deep layers. The fibroblasts are probably involved in elaboration of proteoglycans and collagen, and may also constitute a germinal zone for deeper cartilage.
Elastic cartilage
Elastic cartilage occurs in the external ear, corniculate cartilages, epiglottis. Like hyaline cartilage, it contains typical chondrocytes, either singly or in small groups, surrounded by a matrix rich in type II collagen fibrils. However, the more distant interterritorial matrix is pervaded by very fine yellow elastic fibres containing the protein elastin. A structure is termed ‘elastic’ if it returns to its original shape when loaded and then unloaded.
Elastic fibres (an- cartilage) have the special property of being able to do this even after being subjected to deformations greater than 15%, which would damage collagen fibres. This characteristic is termed elastic
recoil. Elastic cartilage is resistant to degeneration.
MACROSCOPIC ANATOMY OF BONE
Macroscopically, living bone is white. Its texture is either dense like ivory (compact bone) or honeycomb by large cavities (trabecular, cancellous or spongy bone), where the bony element is reduced to a latticework of bars and plates known collectively as trabeculae. Compact bone is usually limited to the outer shell or cortex of mature bones, where it is important in determining their strength and providing rigid articular surfaces. Cortical thickness and architecture vary between and within bones, and generally decrease with age in adults. Trabecular bone provides support to the cortex while minimizing weight. The presence of a large central medullary canal in long
bones also helps to reduce their weight. Spaces within bones provide convenient and secure locations for the storage of haemopoietic tissues and fat. Bone forms a reservoir of metabolic calcium and of phosphate, which is under hormonal and cytokine control.
Trabecular bone provides strength in compression and so is abundant in the epiphyses of long bones, and in the vertebral bodies of the spine.
However, in some bones of the skull, notably the mastoid process of the temporal bone and the paranasal sinuses of the frontal, maxilla, sphenoid and ethmoid bones, many of the internal cavities are filled with air, i.e. they are variably pneumatized.
MICROSTRUCTURE OF BONE
Bone contains a mineralized collagenous extracellular matrix surrounding a range of specialized cells including osteoblasts, osteocytes anosteoclasts. Periosteum, endosteum and marrow are closely associated tissues.
Osteoblasts
Osteoblasts are derived from osteoprogenitor (stem) cells of mesenchymal origin present in bone marrow and other connective tissues. They proliferate and differentiate into osteoblasts prior to bone formation, stimulated by bone morphogenetic proteins (BMPs). A layer of osteoblasts covers the forming surfaces of growing or remodelling bone.
Osteoblasts are responsible for the synthesis, deposition and mineralization of the bone matrix, which they secrete. Once embedded in the matrix, they become osteocytes.
Osteoblasts contain prominent bundles of actin, myosin and other cytoskeletal proteins associated with the maintenance of cell shape, attachment and motility.
Osteoblasts are typical protein-secreting cells. They synthesize and secrete collagens and a number of glycoproteins. Osteocalcin is required for bone mineralization, binds hydroxyapatite and calcium, and is used as a marker of new bone formation. Osteonectin is a phosphorylated glycoprotein that binds strongly to hydroxyapatite and collagen.
Osteoblasts function
Osteoblasts also play a key role in the hormonal regulation of bone resorption. They express receptors for parathyroid hormone (PTH), 1,25-dihydroxy vitamin D3 (calcitriol) and other promoters of bone resorption. When activated, osteoblasts promote osteoclast differentiation via PTH-activated expression of cell surface RANKL, which binds to RANK on immature osteoclasts, establishes cell–cell contact antriggers contact-dependent osteoclast differentiation. In the presence of PTH, osteoblasts also downregulate secretion of osteoprotegerin, a
soluble decoy ligand with higher affinity for RANKL. In conditions favouring bone deposition, secreted osteoprotegerin blocks RANKL binding to RANK, restricting the number of mature osteoclasts.
Osteocytes
Osteocytes are the major cell type of mature bone and are distributed throughout its matrix, interconnected by numerous dendritic processes to form a complex cellular network. They are derived from osteoblasts that have become enclosed within their rigid matrix and so have lost the ability to divide or to secrete new matrix.
(The rigidity of mineralized bone matrix prevents interstitial growth, so that new bone must always be deposited on pre-existing surfaces.)
Extracellular fluid fills the small, variable spaces between osteocyte cell bodies and their rigid lacunae, which may be lined by a variable (0.2–2 µm) layer of unmineralized organic matrix. The same fluid fills the narrow channels or canaliculi that surround the long processes of the osteocytes. Approximately 0.25–0.5 µm wide, the canaliculi provide a route for the diffusion of nutrients, gases and waste products between osteocytes and blood vessels.
In well-vascularized bone, osteocytes are long-lived cells that actively maintain the bone matrix. Old osteocytes may retract their processes from the canaliculi; when they die, their lacunae and canaliculi may become plugged with cell debris and minerals, which hinders diffusion through the bone. Osteocyte death leads to matrix resorption by osteoclast activity. Osteocytes themselves are often mineralized.
Osteoclasts
Osteoclasts are large polymorphic cells containing up to 20 oval, closely packed nuclei. They lie in close contact with the bone surface in resorption bays (Howship’s lacunae).
Functionally, osteoclasts are responsible for the local removal of bone during bone growth and remodelling. They dissolve bone minerals by proton release to create an acidic local environment, and they remove organic matrix by secreting lysosomal (cathepsin K) and non-lysosomal (e.g. collagenase) enzymes. Osteoclasts are stimulated to resorb bone by signals from local cells (including osteoblasts, macrophages and lymphocytes) and by blood-borne factors such as PTH and 1,25-dihy-roxy vitamin D3 (calcitriol). Calcitonin, produced by C cells of the thyroid follicle, reduces osteoclast activity.
Osteoclasts differentiate from myeloid stem cells via macrophage colony-forming units. Differentiation is primarily regulated by two cytokines: macrophage-colony stimulating factor, secreted by osteoblasts, and RANKL, expressed by osteoblasts. The mononuclear precursors fuse to form terminally differentiated multinuclear
osteoclasts. Osteoclast differentiation inhibitors are potential therapeutic agents for bone-loss-associated disorders, e.g. osteoporosis, rheumatoi- arthritis, Paget’s disease, periodontal disease and osteosarcoma.
Woven and lamellar bone
Woven bone and lamellar bone represent two quite distinct types of organization. In woven (or bundle) bone, the collagen fibres and bone crystals are irregularly arranged. Woven bone is typical of young fetal bones, but
is also seen in adults during excessively rapid bone remodelling and
during fracture repair. It is formed by highly active osteoblasts during development, and is stimulated in the adult by fracture, growth factors or prostaglandin E2.
Lamellar bone, which makes up almost all of an adult skeleton, is more organized and is produced more slowly. The precise arrangement of lamellae (bone layers) varies from site to site. In trabeculae and the outer (periosteal) and inner (endosteal) surfaces of cortical bone, a few lamellae form continuous circumferential layers that are more or less parallel to the bony surfaces. However, in more central regions of cortical bone, the lamellae are arranged in concentric cylinders around neurovascular channels called Haversian canals. This interconnecting, three-dimensional, laminated construction increases the toughness of lamellar bone because the interfaces between lamellae are effective in stopping the growth of cracks.
Cortical bone
The cylindrical structural units that comprise most cortical bone are termed Haversian systems or osteons. Osteons usually lie parallel with each other; in long bones, they lie parallel with the long axis of the bone. Irregular gaps between osteons are filled with interstitial lamellae, which are the fragmentary remains of older osteons and circumferential lamellae.
Each osteon is permeated by the canaliculi of its resident osteocytes, which form pathways for the diffusion
of metabolites between osteocytes and blood vessels. The maximum diameter of an osteon ensures that no osteocyte is more than 200 µm from a blood vessel, a distance that may be a limiting factor in their survival.
The central Haversian canals of osteons vary in size. Each canal contains one or two capillaries lined by fenestrated endothelium and surrounded by a basal lamina, which also encloses typical pericytes. The bony surfaces of osteonic canals are perforated by the openings of osteocyte canaliculi and are lined by collagen fibres.
Haversian canals communicate with each other and directly or indirectly with the marrow cavity via vascular (nutrient) channels called Volkmann’s canals, which run obliquely or at right angles to the long axes of the osteons. The majority of these channels appear to branch and anastomose, but some join large vascular connections with vessels in the periosteum and the medullary cavity.
Cement lines are also known as reversal lines because they mark the limit of bone erosion prior to the formation of a new osteon. Canaliculi occasionally pass through cement lines, and so provide a route for exchange between interstitial bone lamellae and vascular channels within osteons.
Basophilic resting lines can occur in the absence of erosion; they indicate where bony growth has been interrupted and then resumed.
Trabecular bone
The organization of trabecular bone (also known as cancellous or spongy bone) is basically lamellar. Trabeculae take the form of branching bars and curved plates of varying width, length and thickness. They are covered in endosteal tissue because they are adjacent to marrow cavities. Thick trabeculae and regions close to compact bone may contain small osteons, but blood vessels do not otherwise lie within trabeculae; osteocytes therefore rely on canalicular diffusion
from adjacent medullary vessels. In young bone, calcified cartilage may occur in the cores of trabeculae, but this is generally replaced by bone during subsequent remodelling.
Periosteum, endosteum and bone marrow
The outer surface of bone is covered by a condensed collagenous layer, the periosteum. The inner surface is lined by a thinner, more cellular endosteum. Osteoprogenitor cells, osteoblasts, osteoclasts and other cells important in the turnover and homeostasis of bone tissue lie in these layers.
The periosteum is tethered to underlying bone by thick collagen fibres (Sharpey’s fibres), which penetrate deep into the outer cortical bone tissue. It is absent from articular surfaces, and from the points of insertion of tendons and ligaments (entheses). The periosteum is highly active during fetal development, when it generates osteoblasts for the appositional growth of bone. Osteoprogenitor cells within the mature periosteum are indistinguishable morphologically from fibroblasts. Periosteum is important in the repair of fractures; where it is absent (e.g. within the joint capsule
of the femoral neck) fractures are slow to heal.
Quiescent osteoblasts and osteoprogenitor cells act as the principal reservoir of new bone-forming cells for remodelling or repair on the endosteal surfaces of resting adult bone. Bone endosteum is likely to be important in calcium homeostasis because it provides a total surface
area of approximately 7.5 m2. It is formed by flattened osteoblast precursor cells and reticular (type III collagen) fibres, and lines all the internal cavities of bone, including the Haversian canals.
Intramembranous ossification
Intramembranous ossification is the direct formation of bone (membrane bone) within highly vascular sheets or ‘membranes’ of condense primitive mesenchyme. At centres of ossification, mesenchymal stem cells differentiate into osteoprogenitor cells, which proliferate around the branches of a capillary network, forming incomplete layers of osteoblasts in contact with the primitive bone matrix. The cells are polarized, and secrete osteoid only from the surface that faces away from the blood vessels. The earliest crystals appear in association with extracellular matrix vesicles produced by the osteoblasts. Crystal formation subsequently extends into collagen fibrils in the surrounding
matrix, producing an early labyrinth of woven bone, the primary spongiosa. As layers of calcifying matrix are added to the early trabeculae, osteoblasts become enclosed within primitive lacunae. These new osteocytes retain intercellular contact by means of their fine cytoplasmic processes (dendrites) and, as these elongate, matrix condenses around them to form canaliculi.
As matrix secretion and calcification proceed, trabeculae thicken and vascular spaces become narrower. Where bone remains trabecular, the process slows and the spaces between trabeculae become occupied by haemopoietic tissue. Where compact bone is forming, trabeculae continue to thicken and vascular spaces continue to narrow. Meanwhile, the collagen fibres of the matrix, secreted on the walls of the narrowing spaces between trabeculae, become organized as parallel, longitudinal or spiral bundles, and the cells they enclose occupy concentric sequential rows. These irregular, interconnected masses of compact bone each have a central canal and are called primary osteons (primary Haversian systems). They are later eroded, together with the intervening woven bone, and replaced by generations of mature (secondary) osteons.
While these changes are occurring, mesenchyme condenses on the outer surface to form a fibrovascular periosteum. Bone is laid down
increasingly by new osteoblasts, which differentiate from osteoprogenitor cells in the depper layers of the periosteum. Modeling of the growing bone is achieved by varying rates of resorption and deposition at different sites.
Endochondral ossification
The hyaline cartilage model that forms during embryogenesis is a miniature template of the bone that will subsequently develop. It becomes surrounded by a condensed, vascular mesenchyme or perichondrium,
which resembles the mesenchymal ‘membrane’ in which intramembranous ossification occurs. Its deeper layers contain osteoprogenitor cells.
The first appearance of a centre of primary ossification occurs when chondroblasts deep in the centre of the primitive shaft enlarge greatly. The intervening matrix is compressed into thin, often perforated septa. The cells degenerate and may die, leaving enlarged and sometimes confluent lacunae (primary areolae) whose thin walls
become calcified during the final stages. Type X collagen is produced in the hypertrophic zone of cartilage. Matrix vesicles originating from chondrocytes in the proliferation zone are most evident in the intercolumnar regions, where they appear to initiate crystal formation. At the same time, cells in the deep layer of perichondrium around the centre of the cartilage model differentiate into osteoblasts and form a peripheral layer of bone. Initially, this periosteal collar, formed by intramembranous ossification within the perichondrium, is a thin-walled tube that encloses and supports the central shaft.
The periosteal collar, which overlies the calcified cartilaginous walls of degenerate chondrocyte lacunae, is invaded from the deep layers of the periosteum (formerly perichondrium) by osteogenic buds. These
are blind-ended capillary sprouts that are accompanied by osteoprogenitor cells and osteoclasts. The latter excavate newly formed bone to reach adjacent calcified cartilage, where they continue to erode the walls
of primary chondrocyte lacunae. This process leads to their fusion into larger, irregular communicating spaces, secondary areolae, which fill with embryonic medullary tissue (vascular mesenchyme, osteoblasts an- osteoclasts, haemopoietic and marrow stromal cells, etc.). Osteoblasts attach themselves to the delicate residual walls
of calcified cartilage and lay down osteoid, which rapidly becomes confluent, forming a continuous lining of bone. Further layers of bone are added, enclosing young osteocytes in lacunae and narrowing the perivascular spaces. Bone deposition on the more central calcified cartilage ceases as the formation of subperiosteal bone continues.
What is remodelling and why is it important?
Stiff materials (including bone) are vulnerable to the accumulation of microdamage during repeated loading. In metals this can result in crack propagation and ‘fatigue failure’. Bone reduces the risk of such failure by periodically renewing itself, one small region of tissue at a time. This process is referred to as ‘remodelling’ because the volume and orientation of newly replaced matrix are not necessarily the same as the old; instead, bone takes this opportunity to adapt its mass and architecture to prevailing mechanical demands. Remodelling affects the local balance between resorption and deposition of bone. Its primary purpose is to renew bone rather than increase its mass, and the process continues throughout life.
Three types of fibrous joints
Three definable subtypes are sutures, gomphoses and syndesmoses
What is a suture (joint)
Sutures are restricted to the skull. In a suture, the two bones are separated by a layer of membrane-derived connective tissue. The sutural aspect of each bone is covered by a layer of osteogenic cells (cambial layer) overlaid by a capsular lamella of fibrous tissue that is continuous with the periosteum. On completion of growth, many sutures synostose and are obliterated. Synostosis occurs normally as the skull ages; it can begin in the early
twenties and continues into advanced age.
Gomphosis
A gomphosis is a peg-and-socket junction between a tooth and its
socket, where the two components are maintained in intimate contact
by the collagen of the periodontium connecting the dental cement to
the alveolar bone. Strictly speaking, a gomphosis is not an articulation
between two skeletal structures.
Syndesmosis
A syndesmosis is a truly fibrous connection between bones. It may be represented by an interosseous ligament (e.g. the interosseous membrane between the radial and ulnar shafts), a slender fibrous cord, or a denser fibrous membrane (e.g. the posterior region of the sacroiliac joint).
CARTILAGINOUS JOINTS
Cartilaginous joints may be classified as primary (synchondrosis) or secondary (symphysis), depending on the nature of the intervening cartilage. While the distinction between fibrous and cartilaginous joints is usually clear, some degree of admixture can occur in which either a predominantly fibrous articulation contains occasional island of cartilage, or a predominantly cartilaginous articulation contains aligned dense bundles of collagen. These joints tend to be less rigid than the fibrous articulations and some permit restricted movement.
Primary cartilaginous joints
Primary cartilaginous joints or synchondroses occur where advancing centres of ossification remain separated by an area of hyaline (but nonarticular) cartilage. They are present in all postcranial bones that form from more than one centre of ossification. Since hyaline cartilage retains the capability to ossify with age, synchondroses tend to synostose when growth is complete. Primary cartilaginous joints are almost exclusively associated with growth plates.
Secondary cartilaginous joints
Secondary cartilaginous joints, or symphyses, are largely defined by the presence of an intervening pad or disc of fibrocartilage interpose between the articular (hyaline) cartilage that covers the ends of two articulating bones. The pad or disc varies from a few millimetres to over a centimetre in thickness, and the whole region is generally bound by strong, tightly adherent, dense connective tissues. Collagenous ligaments extend from the periostea of the articulating bones across the symphysis. The ligaments blend with the hyaline and fibrocartilaginous
perichondria but do not form a complete capsule. The combined strength of the ligaments and fibrocartilage can exceed that of the associated bones. A symphysis is designed to withstand a range of stresses (compression, tension, shear, bending and torsion) but the range of movement is generally limited, both by the physical nature of the articulation and by adjacent bones. Tears are usually the result of sudden stresses that occur when the body is in an inappropriate posture.
