Musculoskeletal System II - Lecture NOTES

Musculoskeletal System II - Lecture NOTES - Musculoskeletal...

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Unformatted text preview: Musculoskeletal System II Bone and Cartilage A. Cartilage I. Cartilage Development Cartilage consists of cells (chondrocytes), water, and an extracellular matrix. Cartilage derivesits form and mechanical properties from the matrix. The cells contribute little (1%) to the volume of the tissue. Cartilage lacks blood vessels, lymphatic vessels, and nerves. Cartilage initially forms from condensations of undifferentiated mesenchymal cells. Induction of the cartilage control gene, SOX9, induces mesenchymal cells to differentiate into chondroblasts which elaborate a cartilage matrix, secreting collagens and proteoglycans. The tissue is recognizable as cartilage when an accumulation of matrix separates individual chondrocytes and they assume a spherical shape. II. Chondroblasts and Chondrocytes The chondroblast forms matrix in actively growing cartilage. During matrix formation chondroblasts become encased within the expanding matrix and isolated from one another. They then appear to be less active and are called chondrocytes. Chondocytes are located within cavities called lacunae within the matrix. Chondrocyte shape varies from discoid to spherical depending on location in the cartilage. Encased in a matrix with no blood supply, chondrocytes exist with a low concentration of oxygen compared to most other tissues. As a result they depend primarily on anaerobic metabolism. The chondrocyte is responsible for maintenance of the cartilage matrix. III. Perichondrium Mesenchyme surrounding cartilage models differentiates into the perichondrium. The perichondrium is composed of a cellular or chondrogenic layer of chondrocytic precursor cells and small blood vessels immediately adjacent to the cartilage, and an outer fibrous layer made of irregularly arranged collagen fibers and fibroblasts. Cartilage is generally always surrounded by perichondrium, except at articular surfaces and in fibrocartilage. IV. Cartilage Growth Interstitial growth: Chondroblasts can undergo several mitotic divisions and after each division new matrix separates the daughter cells. This process leads to considerable expansion of the cartilage from within. Appositional Growth: Occurs in regions where cartilage is surrounded by a perichondrium. Chondroblast precursors from the cellular layer of the perichondrium divide, differentiate and secrete matrix on the cartilage surface. V. Cartilage Matrix The primary components of the extracellular matrix (ECM) are proteoglycans, collagens and water. Other proteins and glycoproteins are present in smaller amounts. These combine to provide the tissue with its complex structure and unique mechanical properties. A meshwork of collagen fibrils gives cartilage its form and tensile strength. Proteoglycans and non-collagenous proteins bind to the collagen lattice or become entrapped within it. Water fills the remaining space in this molecular framework. Non- collagenous proteins are thought to organize and stabilize the macromolecular framework and help chondrocytes to bind to the matrix. Water: Most abundant component of cartilage, 65-80% of the wet tissue weight Contains gases, small proteins, metabolites, and a high concentration of cations to balance the negatively charged matrix proteoglycans. A proportion of the water can move freely in and out of the tissue. Collagens: Contribute about 60% of the dry weight of cartilage Fibrillar network provides tensile stiffness and strength Entraps large proteoglycans. Proteoglycans: Contribute 25—35% of the dry weight of cartilage Two major classes of proteoglycans: Aggrecans: large aggregating proteoglycan monomers. Small proteoglycans: including decorin, biglycan, and fibromodulin. VI. Cartilage Types Three types of cartilage are distinguishable on the basis of different structural characteristics of the matrix: H yaline . Elastic F lbw-Cartilage. a. H yaline Cartilage (means glassy or transparent) Is the most abundant type of cartilage in the adult Found on articulating surfaces of bones Provides support in the nose, larynx, trachea (C-rings) and bronchi Forms the temporary (model) skeleton in the embryo which is replaced by bone during endochondral ossification; in this process it also forms the growth plates. Surrounded by perichondrium except at articular surfaces Extracellular matrix (white in color): Primarily Type II collagen fibers. Functions to sustain intermittent compression b. Elastic Cartilage Found where elasticity as well as rigidity is needed, such as in the epiglottis and external ear and eustacian tubes. Extracellular matrix (yellowish in color): Similar to hyaline but has many dense branching elastic fibers Elastic fibers composed of elastin, to maintain tissue shape Elastic fibers stretch easily but return to their original length. Perichondrium is present. c. F ibrocartilage Located at sites where strength and some resiliency are needed, at transitions between fibrous connective tissue and stiffer tissues such as cartilage and bone e.g. junctions of tendons and ligaments with bone, intervertebral disc, meniscal cartilage, pubic symphysis Matrix is characterized by prominent type I collagen fibrils and less proteoglycan than hyaline cartilage. Generally merges imperceptibly into the neighbouring tissues Perichondrium is absent VII. Cartilage Nutrition - Cartilage is avascular. Chondrocytes depend on diffusion of nutrients through the matrix. Nutrients diffuse either from the synovial fluid in joints or from capillaries outside the perichondrium. In articular cartilage mechanical deformation induces fluid flow in the matrix which enhances nutrient delivery. Nutrients, substrates for the synthesis of matrix molecules, newly synthesized molecules, degraded matrix molecules, metabolic waste products, cytokines and growth factors, all pass through the matrix. B. Bone 1. Types of Bone Two different kinds of bone can be differentiated by their volume fraction or porosity. Most bone tissue is of either very high or very low porosity, with little bone of intermediate porosity. These two types of bone are referred to as cortical bone and trabecular bone, respectively. ‘fi Cortical (Compact) Bone After Cowin. Bone Mechanics Handbook 2001, CRC Press. | Trabecular (Canlous, spongy) Bone a. Cortical Bone (Compact) Cortical bone is dense and solid and it makes up almost 80% of the total skeletal mass. It forms the outer wall of all bones. It has a very low porosity (5-10%) and the only spaces within it are haversion canals, Volkmann’s canals (connect the haversion canals to each other), lacunae (cavities) for osteocytes, canaliculi (tunnels for osteocytic processes) and erosion cavities (transient holes created by osteoclasts during remodeling). Cortical bone is generally made of lamellar bone and has a slow turnover rate. The bulk of cortical bone is found in the shaft of long bones and its functions are generally supportive and protective. b. T rabecular Bone (Cancellous, Spongy) Trabecular bone makes up approximately 20% of the bone mass. It is found in the inner parts of short bones such as the vertebrae, the flat bones and the expanded ends of long bones. It has a very high porosity (70-94%). Trabecular bone is a latticework of bony plates and rods called trabeculae. The trabeculae never form enclosed cells. Instead the pores are interconnected and form structural support for the intervening bone marrow. There is considerable variation in trabecular structure, for example there can be the occasional plate among the struts, or the occasional strut among the plates. In some cases, the plates and struts may be preferentially aligned in one direction. Cancellous bone is usually made of lamellar bone. It has a high turnover rate and functions include structural support and mineral homeostasis. II. Bone Marrow Bone marrow tissue fills much of the available space within the central cavity of bones. It fills the space between blood vessel walls and bone surfaces in the pores of cancellous bone. It is best known as a source of hema i cells but contains many other cell types with varied functions. For example, a 3—D network of cells known as the bone \s adipocytes, osteogenic cells (osteoblasts and preosteoblasts) near bone 5 faces and reticular cells. As well as providing structural support for hematopfgesi , bone marrow stroma is also a source of marrow stromal stem cells. These ce 5, er appropriate stimulation, can mature into diverse populations of cells including fibroblasts, osteoblasts, chondrocytes, adipocytes and smooth muscle cells. These cells are thought to Wortm of oSteoblasts for bone remodeling and repair. V 111. Cells of Bone Bone is composed of 4 different cell types. Osteoblasts, osteocytes and bone lining cells originate from local osteoprogenitor cells. Osteoclasts arise from the fusion of mononuclear precursors which originate in hematopobtic tissues. 9 Blood vessel Osteoblast Osteoclast Q E precursors Osteoprogenitor Osteociast Osteoid—[ Mineralized bone Osteocyte Bilezikian et a1. Principles of Bone Biology 2002. Academic press. a. Osteoblast (7 Q '\ C2113 I )1 UL (ka. v) {FTC Differentiation Bone formation takes place during ergnbrygrmgnfintL growth, remodeling and fracture repair. For this reason it is thought that there is a large r‘éErvoir of cells in the W of osteogenesis throughout life. Bone marrow stroma contains SWHOI‘ cells of skeletal tissues such as bone, cartilage and muscleulnduction of key genes starts a "cascade that leads to the extmmypic genes and commitment to a particular cell lineage. Cells are the then referred to as progenitors e.g. osteoprogenitors. Osteoprogenitors undergo a period of intense proliferation, which then slows as the cells start to differentiate into mature bone cells. Some progenitors are destined to become bone lining cells, some will undergo apoptosis and others will become encased in the matrix they secrete to become osteocytes. Characteristics Osteoblasts are bone forming cells which appear as a layer of contiguous cells which in their active state are cuboidal (15-30um thick). The active osteoblast can be identified on bony surfaces by its morphological and ultrastructural properties which are typical of a secretory cell. These features include a large nucleus, enlarged golgi apparatus, and extensive endoplasmic reticulum. The osteoblast is highly enriched in alkaline phosphatase and secretes type I collagen and specialized bone matrix proteins. Osteoblasts synthesize and secrete unmineralized bone matrix (osteoid) and then participate in mineralization. Bone deposition takes place some time before mineralization and therefore, a layer of osteoid can often be identified. The delay can be up to 10 days leading to an osteoid seam approximately lOum wide. Mteocytes f Osteocytes are former osteoblasts that have become buried in the bone which they and their neighbours have deposited. Osteocytes retain contact with one another via slender cell processes which run through mineralized bony canals, which develop as matrix is laid down around the cell process. These bony canals are called canaliculi. Processes from adjoining cells are connected by gap junctions which allow for communication between cells. Gap junctions are ion channels which allow the passage of ions and signaling molecules directly from cell to cell. Osteocytes are metabolically and electrically coupled through gap junction protein complexes. Gap junctions have been shown to be essential for osteocyte maturation, activity, and survival. Because osteocytes are by far the most abundant of the bone cells, a vast cellular network of communicating cells exists within the bone. It is thought that in healthy bone, osteocytes can reside for long periods, possibly decades. The extent of the osteocytic network and the ability of osteocytes to communicate not only with themselves but with surface osteoblasts has raised the possibility that the primary function of osteocytes is to act as mechanosensors. It is thought that osteocytes may detect mechanical loads in the bone matrix and communicate signals to surface osteoblasts to initiate either bone deposition or resorption as determined by the load that the bone is experiencing. The ability of bone to change its structure to meet certain functional requirements is called adaptation. c. Bone Lining Cells Osteoblasts that do not become encased in the bone matrix remain on the surface when bone formation ceases and are known as bone lining cells. These cells are easily distinguished from active cuboidal osteoblasts since they are flat, elongated and largely quiescent with few organelles. Bone lining cells are found on resting bone surfaces that are undergoing neither resorption nor formation. Lining cells communicate with one another and with osteocytes via gap junctions. d. Osteoclasts Osteoclasts are multinucleated giant cells that resorb bone. They develop from hematopoietic cells of the monocyte/macrophage line. Osteoclast development occurs within the local bone environment as it requires the presence of either osteoblasts or stromal cells. Upon arrival at the bone surface, the osteoclast undergoes characteristic changes in morphology. Firstly a dense ring of actin forms which is tightly anchored to the bone matrix via integrins, effectively forming a sealed area of membrane underneath the cell. Within the actin ring the cell membrane startsy’Lruffle due to the fusion of many intracellular vesicles. This ruffled border is the resorbing organ of the osteoclast. After formation of the sealing zone and elaboration of the ruffled border, the osteoclast proceeds to acidify the resorption lacunae by pumping protons through the ruffled border. Pumping of protons is balanced by secretion of chloride ions. The low pH causes solubilization of the mineral within the matrix. Proteolytic enzymes are secreted into the resorption lacunae which degrade the organic matrix. Degradation products are endocytosed, across the cell and are released from the functional secretory domain, which is a specialized region of the cell membrane located on the basal membrane. Many small vesicles can be identified in the cytoplasm that transport enzymes toward the bone matrix and internalize partially digested bone matrix. At least in vitro the cell can undergo more than one cycle of bone resorption i.e. attachment, polarization, resorption and detachment. Eventually the osteoclast will undergo apoptosis and die. ' IV. Bone Matrix The composition of bone varies with age, anatomic location, diet, and health status. However, in general, adult mammalian bone is assembled as follows: 50-70% mineral 20—40% organic matrix 5-10% water < 3% lipid. (1. Organic Bone Matrix Bone accounts for the largest proportion of the body's connective tissue mass. The major component (approximately 90%) of the organic bone matrix is type I collagen. Noncollagenous proteins (NCPs) compose the remaining 10% of the bone protein content. b. Mineral The mineral of bone is called hydroxyapatite [Ca10(PO4)6(OH)2] and it contributes mechanical rigidity and load bearing strength to the bone composite. Bone mineral crystals are extremely small (200 A in their largest dimension) compared to large geologic hydroxyapatite crystals. In addition bone mineral contains numerous impurities (carbonate, magnesium, acid phosphate). These small imperfect crystals are more soluble than geologic apatite, enabling bone to act as a reservoir for calcium, phosphate, and magnesium ions. Individual hydroxyapatite crystals are rods or plates with a hexagonal symmetry. V. Bone Tissue Types There are two major types of bone tissue: ' a. Woven bone: Formed quickly Poorly organized tissue, collagen fibers, osteocytes and mineral crystals are randomly arranged. Weaker than lamellar bone, becomes highly mineralized to compensate Generally a provisional material that is replaced by lamellar bone. b. Lamellar bone: Slowly formed Highly organized bone consisting of parallel layers or lamellae of collagen and mineral. Lamellae contain fibers that run in approximately the same direction. Orientation of fibers in adjacent lamellae may change up to 90° A B - A. Schematic representation ofthe change in orientation of collagen fibers in adjacent lamellae. Martin et al. Skeletal Tissue Mechanics (1998) Springer Verlag. B. Lamellar structure gives rise to birefringence which is an optical property of a material that rotates the plane of polarized light. Under polarized light laminations appear as alternating dark and light layers. Cowin, Bone Mechanics Handbook, (2001) CRC Press. ...
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Musculoskeletal System II - Lecture NOTES - Musculoskeletal...

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