OST 521 Lecture 2: Cartilage and Bone

Mesenchymal stem cells

these cells are highly proliferative and differentiate into chondrogenic precursors

Chondrogenic precursors

these cells differentiate into chondroblasts

Chondroblasts

these cells synthesize cartilage and the ECM and can further differentiate into chondrocytes

Chondrogenesis

cartilage growth and development

Perichondrium (location)

this dense irregular connective tissue covers all hyaline surfaces except articular joints

Perichondrium (purpose)

this tissue contains blood vessels that nourish avascular hyaline and elastic cartilages

Perichondrium (appearance)

the inner layer of this tissue contains spindle shaped chondroblasts

Interstitial growth

this type of growth occurs from within an existing cartilage and occurs when existing chondrocytes enlarge and divide

Osteochondroma

pathologic overgrowth of cartilage and bone near the growth plate

Interstitial growth (location)

this type of growth occurs at growth plates, in the embryo as the skeletal template, and on articular cartilage

Appositional cartilage growth

this type of growth occurs at the periphery through differentiation of perichondrial cells

Hyaline cartilage (image)

Fibrocartilage (location)

this type of cartilage is found in the vertebral column, pubic symphysis, menisci, intervertebral discs, and the sites of insertion of tendon/ligament on bone

Fibrocartilage (histology)

chondrocytes in this tissue are aligned in rows between parallel bundles of type I collagen and surrounded by a small amount of matrix

Nucleus pulposus

fibrocartilage in this structure has a matrix rich in hyaluronic acid and type II collagen

Fibrocartilage (image)

Hyaline cartilage (location)

this type of cartilage can be found on joint surfaces, bronchial walls, costal cartilages, embryonic bone template, nose and septum

Hyaline cartilage

this type of cartilage can undergo both appositional and interstitial growth in utero and childhood, then persist as quiescent cells in adulthood

Hyaline cartilage (purpose)

this type of cartilage allows smooth movement of the joints

Hyaline chondrocytes

these cells appear small and elongated at the joints surface and large and rounded in deep cartilage

Elastic cartilage (location)

this type of cartilage is found at the tip of the nose, external ear, walls of the external auditory and eustachian canals, the epiglottis, and the true vocal folds

Elastic cartilage (gross appearance)

this cartilage is opaque, yellow, and flexible

Elastic fibers

these fibers are made mostly of elastin with some fibrillin

Synovial membrane

this layered structure is found on the non-articulating surfaces of the synovial cavity

Synovial fluid

this substance nourishes hyaline cartilage at articulating joints

Articular cartilage (contents)

this type of cartilage is made of type II collagen fibers and hyaluronic acid

Articular cartilage

this type of cartilage is nourished by metabolite exchange in synovial fluid, powered by joint movement

Synoviocytes

these cells can be divided into fibroblast-like and macrophage-like

Fibroblastic synoviocytes

these cells produce synovial fluid

Macrophagic synoviocyes

these cells engulf debris

Chondrodystrophies

disturbances in cartilage growth

Achondroplasia

this inherited condition decreases chondrocyte proliferation at growth plates, causing dwarfism with normal trunk size

Rheumatoid arthritis

this condition is characterized by chronic inflammation of synovial membranes lining joints, allowing lymphocyte infiltration, joint capsule thickening, pain, and degeneration

Osteoarthritis

this degenerative condition causes articular cartilage to thin and crack, affecting subchondral bone

Osteoarthritis (causes)

this degenerative condition is caused by chronic stress, aging, or injury and occurs in fingers, knees, and hips

Chondrosarcoma

these malignant neoplasms arise from cartilage or cartilage transformed bone

Perichondrial cell invasion

this process of repairing cartilage produces a dense connective tissue scar

Hyaline cartilage degeneration

this process involves the enlarging and death of chondrocytes and calcification of the matrix

Partial (chondral) damage

this type of cartilaginous damage doesn't penetrate the subchondral bone

Full thickness (osteochondral) damage

this type of cartilaginous damage penetrates the subchondral bone

Early onset degenerative osteoarthritis

this condition develops when traumatic cartilaginous lesions heal, forming fibrocartilage

Factors favoring degeneration

immobility, not mitotically or metabolically active, hypoxia, poor diffusion, avascular

Factors hindering degeneration

weight bearing activities and controlled compression

Microfracture

this type of marrow stimulation makes holes in the damaged cartilage and introduces marrow cells

Non-surgical cartilaginous repair

these processes include microfractures, marrow stimulation, osteochondral auto or allografting, synthetic polymers, and stem cell therapy

Primary bone (location)

aka immature or woven bone, this is the first bone formed during fetal development, young children, healing, and pathologic conditions

Primary bone (contents)

this type of bone contains osteocytes and type I collagen fibers

Secondary bone

aka mature or lamellar bone, this bone is made of concentric lamellae

Lacunae

microscopic spaces in bone that contain osteocytes

Canaliculi

these tunnels connect the osteocytes in lacunae to one another

Haversian canal (structure)

this structure is found at the center of concentrically arranged lamellae

Haversian canal (contents)

this structure contains the blood vessels and nerves required for long bone growth and matrix secretion

Volksman canals

these structures are perpendicular to Haversian canals and connect osteons

Compact bone

aka cortical bone, this type of bone is the hard external layer found in all bones

Osteons (location)

these structures run parallel in compact bone around Haversian canals

Osteons (structure)

this structure is made of a mineral matrix and contain osteocytes

Spongy bone (structure)

aka trabecular/cancellous bone, this light weight bone is made of interlocking networks of trabeculae

Spongy bone (location)

this type of bone is the inner most layer of all bones

Spongy bone (contents)

this type of bone contains red marrow, and NO osteons

Osteoprogenitor cells (OPCs)

these stem cells are located in periosteum and endosteum, and are active during bone development and remodeling

Bone lining cells

these flat, quiescent osteoblasts are on the surface of bones

Osteoblasts (structure)

these cuboidal cells are connected to their neighbors by lateral processes

Osteoblasts (products)

these cells synthesize type I collagen, osteopontin, and osteoprotegrin

Osteoblasts (receptors)

these cells act as membrane receptors for hormones and cytokines

Osteocytes (origin)

these cells arise from mature osteoblasts that become trapped by calcified matrix in lacunae

Osteocytes (structure)

these cells have extensions withing canaliculi that receive nutrients and signals from blood vessels

Osteocytes (communication)

these cells communicate with each other through gap junctions between their extensions

Osteoclasts (origin)

these large, multinucleated cells are derived from pluripotent hematopoietic stem cells

Osteoclasts (structure)

these cells have a ruffled membrane at their apical border that extends into the osteoid to engulf digested products

Osteoclasts (action)

these cells remove calcified matrix with lysosomal proteases and solubilize hydroxyapatite by releasing protons from their ruffle border

Howship's lacuna

these structures are made when osteoclast lysosomal proteases dissolve osteoid

Bone matrix organic contents

proteoglycans, type I collagen, osteopontin, osteocalcin, and ground substance comprise this structure

Ground substance

this part of the bone matrix consists of 2 glycosaminoglycans: keratin sulfate and chondroitin sulfate

Bone matrix inorganic contents

hydroxyapatite, citrate, carbonate, and the hydration shell comprise this structure

Ossification

this process begins by weaving bone from a template, then replacing it with harder concentric lamellar bone

Intramembranous ossification

this process begins in 8 week old embryos and involves proliferation of OPCs in ossification centers

Embryonic mesenchyme

osteoblasts arise from this structure

Osteoblasts (intramembranous ossificiation)

these cells secrete osteoid, which calcifies, trapping the cells and turning them into osteocytes

Ossification centers

these structures fuse during bone development, forming spongy bone

Spongy bone (intramembranous ossification)

the outer layers of this structure are remodeled into compact bone, while the inner layers remain unchanged

Condensed mesenchyme

the remaining unossified part of this structure will become endosteum and periosteum

Endochondral ossification (location)

this process takes place on hyaline cartilage templates, and is used to form all bones except the skull, mandible, and clavicles

Endochondral ossification (process)

bone collars form around the cartilaginous template, dissolving it and forming an ossification center where vessels and OPCs will reside

Primary ossification center

this structure develops along the diaphysis during fetal development

Secondary ossification center

this structure develops later in the epiphyses during childhood

Epiphyseal growth plates (location)

this cartilaginous structure separates primary and secondary ossification centers in long bones

Epiphyseal growth plates (structure)

this structure acts as a scaffold and contains active chondrocytes that allow bone elongation (can last 20 yrs)

Ossification center fusion

this process occurs when the epiphyseal plate disappears and full height is attained

Reserve zone

aka zone 1, this zone contains small flat quiescent chondrocytes

Zone of proliferation

aka zone 2, this zone contains mitotically active chondrocytes that produce daughter cells in stacks/columns

Zone of maturation and hypertrophy

aka zone 3, in this zone chondrocytes and lacunae enlarge, accumulate glycogen and lipids, then breakdown, releasing alkaline phosphatase

Calcified cartilage zone

aka zone 4, dying chondrocytes compress the matrix and trigger CaPo4 deposition and dead chondrocytes are reabsorbed, leaving behind lacunae, which get invaded by blood vessels

Ossification zone

aka zone 5, in this zone osteoblasts line up on spicules of calcified cartilage and secrete osteoid, which mineralizes to form primary bone

Bone lengthening by interstitial growth

undifferentiated cells in the hyaline epiphyseal growth plate mature and calcify, moving from the epiphysis to the diaphysis in this process

Bone widening by appositional growth

aka radial growth, this process begins with formation of a bone collar to which layers of compact bone are added to the periosteum by osteoblasts, and bone is broken down at the endosteum by osteoclasts, enlarging the marrow cavity and lightening bones

Parathyroid hormone (PTH)

this hormone promotes bone resorption (breakdown), increasing osteoclast activity, releasing calcium into the blood

Calcitonin

this hormone opposes PTH by lowering blood calcium levels and promoting bone formation

RANK (receptor activator of nuclear factor kB)

this receptor is present on immature osteoclasts

RANKL (RANK ligand)

this ligand is expressed by osteoblasts

OPG

this ligand is secreted by osteoblasts and osteogenic stromal cells, inhibiting bone resorption by binding with high affinity to RANKL, preventing RANK-RANKL complex formation