Cartilage and Bone

Endochondral ossification IV

Blood vessels and pre-osteoblasts invade degenerating cartilage

Histogenesis of bone

Bone can form either by intramembranous ossification or endochondral ossification

Endochondral ossification

Bone forms by replacement of cartilage model

Intramembranous ossification

Bone forms directly from CT proper. Clusters of mesenchymal cells within CT differentiate into osteoblasts. Cluster of osteoblasts synthesizes a spicule of bone. As spicules enlarge, they fuze and form primary woven bone which is remodeled to form mature bone

Glycoproteins in bone

Bone has some specific bone- or calcified-. Regulates Ca phospate crystal formation. Multiadhesive glycoproteins that bind hydroxyapatite, collagen, and osteocytes.

Synostosis

Two bones fused along suture line. Bones are rigidly joined so no movement occurs

Synchondrosis

Two bones joined by hyaline cartilage or fibrocartilage

Bone collagen

Type I collagen. No elastic fibers. Only fibrillar proteins. Most of organic bone is collagen.

Zone of hypertrophy

chondrocytes increase in size and accumulate glycogen prior to degenerating

Synovial cavity

Space between two bones which is filled synovial fluid. No EP lining of cavity.. May be layer of loose CT or adipose tissue interposed between fibrous capsule and synovial membrane.

Canaliculi

Spaces in matrix that contain osteocyte processes. Little tubes that extend through calcified matrix and connect adj lacunae. Osteocyte processes from adj cells meet and form gap junctions within canaliculi. These connections allow nutrients to move osteocyte-to-osteocyte in otherwise impermeable calcified matrix.

Osteocytes shape

Squamous cells (flattened) and reside within lacunae in calcified bone matrix. Space (hole) in the matrix that contains the cell is known as lacuna. Osteocyte completely fills lacuna. Lacunae are found at boundaries between lamellae.

Endochondral ossification VI

remodeling of bone and underlying calcified cartilage results in replacement of calcified cartilage by bone

Osteoblasts shape

Active osteoblasts are cuboidal or columnar cells with prominent RER and GA. Actively secretes osteoid (uncalcified bone matrix), ions, enzymes, and vesicles involved in calcification of matrix. Inactive osteoblasts are squamous.

Appositional growth

Addition of both cartilage matrix AND chondrocytes to surface of cartilage

Chondrocytes embedded in matrix

Always embedded within cartilage matrix. Only cells normally found within cartilage matrix. Spaces in matrix occupied by cells are lacunae. Chondrocyte completely fills lacuna. (chondrocytes sometimes shrink during fixation of tissue so can create artificial space around cell.

Growth of long bones

Articular surfaces on both distal and proximal ends of long bones. Presents problems: bone can only grow by appositional growth, appositional growth only occurs where osteoblasts are formed from overlying periosteum, and these long bones cant inc in length by adding new bone matrix to surface of bone.

Isogenous group of chondrocytes

As a chondrocyte divides and has multiple daughter cells that are closely-related, they are all descendants of a single chondrocyte and that is an isogenous group

Chondroblasts differentiate into chondrocytes

As chondroblasts secrete matrix, some cells become surrounded by matrix (no longer at boundary). Chondroblasts that become embedded within cartilage differentiate into chondrocytes.

Other lamellar structures

Besides to Haversian systems there are others in mature bone: Outer circumferential lamellae, inner circumferential lamellae, interstitial lamellae.

Bone matrix

Bone is ECM and cells. ECM is inorganic ions (Ca phosphate crystals) and organic components. Organic components are fibrillar proteins (collagen), GAGs, and proteoglycans, and glycoproteins.

Osteocyte secretions

Bone matrix is rigid so interstitial growth is impossible. Osteocytes dont secrete too much organic matrix. Rather involved in deposition and mobilization of Ca from matrix. As bone matures, it becomes more heavily mineralized and this increase in mineralization is a function of osteocytes

Synarthrosis

Bones are physically connected, little or no movement is allowed. Divided into synostosis, synchondrosis, syndesmosis

Outer and Inner surface of bones

Both are remodeled; new layers o bone laid down on these form outer and inner circumferential lamellae. However, most remodeling occurs within substance of bone by a small cylindrical core of bone removed (osteoclasts) and replaced by osteoblasts. This forms Haversian systems

Limited diffusion of bone

Calcification of bone limits diffusion. Bone is vascular with blood vessels running through channels within bone. Also osteocytes are joined with gap junctions.

Bone

Calcified matrix of organic and inorganic substances

Inorganic matrix

Calcium phosphate (hydroxyapatite) crystals are deposited within and alongside collagen fibers in bone. Filling spaces between collagen fibers with Ca phosphate crystals makes bone rigid and ability to withstand compressive force.

Chondrocytes

Capable of cell division. Can arise by differentiation from chondroblasts or division of pre-existing chondrocytes. Both daughter cells initially reside in same lacuna. Secretion of cartilage matrix by daughter cells will divide/separate lacuna.

Hyaluronic acid and proteoglycans

Cartilage has extensive ground substance. Principal proteoglycan consists of large core protein covalently linked to chondroitin sulfate and keratan sulfate molecules (GAGs). Proteoglycans bind to hyaluronic acid (large complex) which carries a large negative charge so it binds cations and water and forms a hydrated gel. This gel provides resistance to compressive forces and allows nutrients to diffuse into cartilage.

Cartilage growth

Cartilage matrix is a pliable gel and can increase in size in 2 ways: appositional growth or interstitial growth

Zone of reserve cartilage (resting zone)

Cartilage on epiphyseal end of epiphyseal plate is quiescent. Chondrocytes in region arent actively undergoing mitosis, adding new matrix, or changing their state of differentiation.

Gross features of bone

Central cavity (marrow cavity) filled with non-bony CT. Compact bone surrounds marrow cavity. Extending from compact bone into marrow cavity are series of spicules and trabeculae of bone called cancellous bone.

Endochondral ossification I

Chondroblasts and chondrocytes first form cartilaginous version of skeletal element

Cells in cartilage

Chondroblasts and chondrocytes. Cells in other CT are not seen in cartilage.

Zone of proliferation

Chondrocytes actively divide Direction of growth is parallel to long axis of bone, proliferation of chondrocytes produce columns of isogenous cells. Chondrocytes actively secrete cartilage matrix resulting in spacing between isogenous chondrocytes increasing as cells get closer to next region

Zone of calcification

Chondrocytes alter composition of cartilage matrix and degenerate. Changes in composition of cartilage matrix allows hydroxyapatite crystals to form within cartilage

Endochondral ossification III

Chondrocytes in cartilage beneath membranous bone hypertrophy and then degenerate. During this process, hypertrophic chondrocytes also modify cartilage matrix so that it calcifies.

Interstitial growth

Chondrocytes way of growing. Matrix increases by increasing number of cells and amount of matrix from within tissue (not adding on like appositional). As cartilage matrix is secreted, the tissue increases in size and distance between chondrocytes increases (less mature matrix adj to each chondrocyte is territorial matrix)

Endochondral ossification II

Collage of bone forms around middle of cartilage by intramemebranous bone formation (from osteoblasts derived from mesenchymal cells within perichondrium)

Cartilage matrix components

Collagen, glycosaminoglycans (GAGs), proteoglycans, and multiadhesive glycoproteins

Cartilage

Connective tissue. Avascular. Nutrients come from blood vessels surrounding the tissue and diffuses through highly hydrated cartilage matrix to reach cells (chondrocytes) which are embedded within cartilage matrix

Remodeling of bone

Constantly being remodeled: osteoclasts constantly removing while osteoblasts replace.

Osteoclasts

Degradation of bone matrix. Large multi-nuceated cells found at boundary between bone and adj CT. Formed by fusion of monocyte-like bone-marrow-derived cells. Osteoclasts related to macrophages. Each osteoclast is a fusion of multiple preosteoclasts so multiple nuclei.

Chondroblasts origins

Derived from mesenchymal cells in perichondrium. Mesenchymal cells will differentiate into chondroblasts and synthesize proteins (type II) and GAGs. capable of cell division so can arise from pre-existing chondroblasts.

Osteocyte nutrients

Diffusion of nutrients through calcified matrix is impossible, so each osteocyte extends narrow processes that connect (via gap junctions) to ends of equivalent processes from adj osteocytes.

Rate of growth in epiphyseal plate

During late adolescene, rate of formation of new cartilage within plate decreases relative to rate of conversion of cartilage to bone. Epiphyseal plate is eventually obliterated and longitudinal growth of bone ceases.

Formation of Haversian system III

Each time osteoblasts change orientation of collagen fibers (thus starting a new lamella), some osteoblasts become trapped within matrix and become osteocytes. Osteocytes remain connected to each other and to osteoblasts via cellular processes extending through canaliculi in newly formed bone. Thus, wall of system will have concentric lamellae of bone matrix with osteocytes aligned along boundaries between lamellae

Elastic cartilage and Fibrocartilage

Elastic cartilage contains elastic fibers. Fibrocartilage contains type I collagen fibers. Matrix of these cartilages still have glassy look but fibers can be seen running through the matrix.

Elastic cartilage

Few skeletal structures like cartilages of external ear, auditory tube, epiglottis. Presence of elastic fibers embedded within cartilage matrix. Synthesized by chondrocytes. Can be seen in microscope. Distinguished from hyaline because chondrocytes are larger and more closely spaced. Surrounded by perichondrium.

Fibrocartilage

Few structures like annulus fibrosus of intervertebral discs, pubic symphysis, articular disks of temporomandibular and sternoclavicular joints, and at points of attachment of ligaments or tendons to cartilage.

Inner circumferential lamellae

Formed on inner surface of bone by osteoblasts derived from endosteum

Outer circumferential lamellae

Formed on outer surface of bone by osteoblasts derived from periosteum

Osteoblasts location

Forms a layer of cells between CT proper (periosteum or endosteum) and bone matrix.

Formation of Haversian system I

Group of osteoclasts "tunnel" into pre-existing bone, eroding a long cylindrical cavity and forms the canal. Osteoclasts clustered at "front-end" of "tunnel". Behind osteoclasts, loose CT containing capillary loop grows into space created by osteoclasts. Blood vessels within Haversian canal arose from transverse, arger blood vessels called Volkmann's canals (no concentric lamellae surrounding Volkmann's)

Types of cartilage

Hyaline cartilage Elastic cartilage Fibrocartilage

Lamellae

In mature bone, matrix is organized into layers called lamellae. Within a lamellae, collagen fibers and crystals oriented parallel to each other. And layer to adj layer, fibers/crystals oriented 90 degrees. Plywood arrangement. Makes bone less brittle. Alternating orientation makes fractures less likely.

Chondroblast appearance

Intermediate between fibroblasts and chondrocytes. Elongated but more rounded than fibroblasts. Actively secreting cartilage matrix (meaning more RER and larger GA than mesenchymal cells).

Multiadhesive proteins

Involved in attaching chondrocytes to cartilage matrix and in cross-linking collagen and GAGs

Osteocytes

Involved in maintenance of bone matrix. Found only within bone matrix. Osteoblasts differentiate into osteocytes.

Chondrocytes shape

Large, round/oval cells. Becomes more round as they get further from edge of cartilage. Secretes cartilage matrix.

Cartilaginous skeletal structures

Laryngeal and tracheal cartilages, nasal cartilages, costal cartilages, and intervertebral disks. Also found on articular surfaces of synovial joints

Articular capsule

Lateral to cavity is a capsule of CT that encloses synovial cavity. Consists of outer layer of dense CT and inner layer (synovial membrane) which is a more cellular layer containing fibroblast-like cells and macrophage-like cells.

Perichondrium

Layer of dense CT that surrounds cartilage. Because cartilage is avascular, perichondrium has blood vessels which provide nutrients for cartilage. Source of mesenchymal cells that differentiate into chondroblasts. Articular surface of articular cartilage, surfaces of cartilage continuous with bone, and fibrocartilage are NOT covered by perichondrium.

GAGs in bone

Little organic ground substance (GAGs). Most space in bone where GAGs and proteoglycans would be is filled with Ca phosphate crystals. Principal function of GAGs and glycoproteins provides resistance to compression so since Ca does that already, no GAGs in bone

Organic matrix

Modified dense CT. Mature/lamellar bone is analogous to dense regular CT. Immature/woven bone is analogous to dense irregular CT. Type I fibers give bone tensile strength.

Calcium phosphate

More than half of dry weight of bone is inorganic ions, specifically calcium phosphate in hydroxyapatite crystals. Crystals form within gaps in collagen fibrils as well as along sides of collagen fibers.

Haversian systems or Osteon

Most lamellae organize as concentric cylinders surrounding a "canal" of loose CT containing blood vessels. This tube is Haversian canal. Together with concentric lamellae of bone surrounding the canal is the Haversian system or osteon

Synovial joint

No perichondrium covering the articular cartilage and the cartilages of opposing bones are separated by thin layer of synovial fluid

Chondroblasts location

ONLY at boundary between perichondrium and cartilage

Formation of Haversian system II

Osteoblasts differentiate from mesenchymal cells within CT in resorption cavity. Osteoblasts line-up along walls of cavity and begin to secrete bone matrix. Secretion of matrix by osteoblasts will thicken the walls of canal and decrease diameter. Newly-formed Haversian systems have canals with large diameters which will shrink as system matures. When diameter is at minimum, osteoblasts stop secreting matrix

Endochondral ossification V

Osteoblasts differentiate on surface of calcified cartilage and begin synthesizing bone

Zone of ossification

Osteoblasts synthesize layer of bone over calcified cartilage. Once bone matrix lays down on top of calcified cartilage matrix, osteoclasts and osteoblasts remodel calcified tissue. Calcified cartilage is removed during this remodeling

Cells of bone

Osteoblasts, Osteocytes, and Osteoclasts

How osteoclast degrade bone matrix

Osteoclast attaches to bone to form a pocket between osteoclast and bone. Osteoclast membrane overlying this pocket transports H+ ions into space, creating acidic environment into which osteoclast secretes lysosomal enzymes. This enzyme degrades organic matrix and low pH solubilizes the Ca phosphate.

Connective tissue coverings

Periosteum surrounds bone. Dense CT. Endosterum, layer of CT, also lines surface of bone facing marrow cavity.

Type II collagen

Principal type of collagen found in cartilage. Forms thin fibrils (67 nm collagen striations). Do not combine to form fibers. Collagen fibrils form network (tensile strength). Cartilage doesnt contain type I or III collagen.

Interstitial lamellae

Remnants of older Haversian systems which have been partially obliterated by formation of more recent Haversian system

Osteoclasts function

Resorption of bone. Often seen in depressions on bone surfaces because of digestion of bone matrix.

Growth plates and epiphyseal plates

Retention of regions of cartilage within ossifying bone (growth plates, epiphyseal plates, or physeal plates). Growth occurs through interstitial growth within cartilaginous epiphyseal plates which is converted into bone through endochondral ossification. As a child, thickness of epiphyseal plate remains constant because growth of cartilage (interstitial growth) is balanced by conversion of cartilage to bond (steady state).

Osteoblast secretions

Secretes bone matrix onto surface of bone resulting in appositional growth of bone. Because calcified matrix is rigid, bone cant grow by interstitial growth. Some osteoblasts become trapped within secreted matrix and differentiate into osteocytes.

Appositional growth of cartilage

Secretion of matrix by chondroblasts increases cartilage size through addition of material to edges of tissue. As matrix is added, some chondroblasts become separated from perichondrium and embedded in cartilage matrix and differentiate into chondrocytes.

Joints

Synarthrosis and Diarthrosis

Diarthrosis

Synovial joint where articular surfaces of 2 bones are covered with hyaline cartilage.

Osteoblasts

Synthesis of bone matrix. Found only at boundary between bone matrix and adj connective tissue. Derived from mesenchymal cells (preosteoblasts/osteoprogenitor cells) found within periosteum and endosteum and CT of Haversian canals. Osteoblasts can form by differentiation of fibroblast-like mesenchymals or by pre-existing cells mitosis.

Syndesmosis

Two bones are joined by dense CT

Histological appearance of cartilage matrix

Type II collagen fibrils are not apparent in matrix of hyaline cartilage (too small). Hyaline cartilage has smooth/glassy but is not uniform. Regions of matrix near chondrocytes are TERRITORIAL matrix (higher rate of turnover, different chemical composition, thinner collagen fibrils, and differential staining properties). Interterritotial matrix is more distant from chondrocytes.

Hyaline cartilage

Typical cartilage. Cartilage matrix doesnt have visible fibers in microscope so tissue has smooth/glassy appearance. Surrounded by perichondrium except on synovial surfaces of articular cartilage or when attached directly to bone (no CT separating epiphyseal plate from adj bone)

Primary/woven/immature bone

When bone is first formed, collagen fibers (and hydroxyapatite crystals) are interwoven so collagen fibers/hydroxyapatite crystals arent parallel. No preferred orientation to the fibers.

Secondary/lamellar/mature bone

When primary bone is replaced, new bone is laid down in layers (lamellae) where all collagen fibers have same orientation (parallel). Intervally, osteoblasts switch orientation of fibers forming new lamella (plywood). This increases strength and decreases brittleness.

Five regions of epiphyseal plate

Zone of reserve cartilage (resting zone) Zone of proliferation Zone of hypertrophy Zone of calcification Zone of ossification

Chondroblasts

found only on surfaces of cartilage, adjacent to perichondrium. not found within cartilage matrix. secretes cartilage matrix.

Fibrocartilage II

intermediate between dense CT and cartilage. Large bundles of type I collagen fibers and fibroblasts. Between bundles of collagen are clusters of chondrocytes embedded within cartilage matrix (type II). No perichondrium surrounding because of dense CT penetration.