Cartilage and Bone Flashcards
What do cartilage and bone have in common? How can they be differentiated?
Both
Abundant extracellular matrix
Cells inhabit spaces called lacunae
Bone
Vascular
Calcification
Stiff
Cartilage
Avascular
Resists calcification
Flexible
Undifferentiated cells that can differentiate into chondroblasts. What’s their significance?
Chondrogenic cells
They form the perichondirum
Mature cells of cartilage
Chondrocytes
How does avascular cartilage receive nutrients?
By diffusion through ECM
What type of cells do chondrogenic cells differentiate into?
Chondroblasts
Are chondroblast mature or immature?
Immature
From where are chondroblast derived?
Mesenchymal cells
Components of chondroblasts
Lipids
Glycogen
Well-developed rER
Golgi Appatatus
What are the two types of cartilage growth? What are characteristics of each?
Interstitial growth (replacing hyaline cartilage)
- Mainly in immature cartilage
- Chondroblasts in existing cartilage divide and form small groups of cells which produce matrix to become separated from each other
Appositional growth (addition of new layers)
- Also in mature cartilage
- Mesenchymal cells surrounding the cartilage in deep part of perichondrium (chondrogenic layer) differentiate into chondroblasts
Chondrogenesis pathway
- Chrondroblasts produce and deposit type II collagen fibers and ECM
- Chrondroblasts are separated and trapped within spaces in the matrix
Each isogenous group is enveloped by a __________matrix and separated by a ___________ matrix.
Territorial; interterritorial
3 types of cartilage. Characteristics of each.
Hyaline cartilage
- Avascular
- Perichondrium – absent in articular cartilage
- Chondrocytes, ECM with type II collagen
Elastic cartilage
- Avascular
- Perichondrium
- Chondrocytes, ECM with type II collagen and elastic fibers
Fibrocartilage
- Generally avascular
- No perichondrium
- Chondrocytes and fibroblasts surrounded by type I collagen
How do fetuses and adults differ in terms of hyaline cartilage?
Fetus: Hyaline cartilage forms most of fetal skeleton before being reabsorbed and replaced by bone during endochondral ossification
Adults: Hylaine cartilage persists in adults as nasal, laryngeal, tracheobronchial, costal cartilage, and articular surface of synovial joints
What is the role of the perichondrium? What is the exception?
Covers surface of hyaline cartilage, except articular cartilage
Layers of perichondrium
- Outer fibrous layer: contains bundles of type I collagen and elastin
- Inner chondrogenic layer: formed by flat chondrogenic cells that can differentiate into chondroblasts
Which type of cartilage cells are active? Which type are not?
Chondroblasts are active
Chondrocytes are not active
Components of the ECM of hyaline cartilage
Aggrecan (proteoglycan)
- Chondroitin sulfate (GAG)
- Core proteins
- Link proteins that bind to hyaluronic acid
Collagen II fibers
Role of aggrecan
Attracts nutrients and water that diffuse through acascular matrix via mechanical pressure
- Mechanical pressure exerted: water leaves cartilage matrix
- Mechanical pressure removed: water returns to cartilage matrix
Where can elasic cartilage be found?
ONLY in auricle and epiglottis
What differentiates elastic cartilage from hyaline cartilage?
Presence of elastic fibers
*Makes elastic cartilage very flexible and able to regain its original shape after deformation
Which cartilage type allows for the connection to bone?
Fibrocartilage
How does fibrocartilage differ from hyaline cartilage?
- ECM: type I collagen fibers, low concentration of proteoglycans and water
- Lacks perichondrium
Intermediate between hyaline cartilage and dense connective tissue
Fibrocartilage
What parts of the body contain fibrocartilage?
Forms part of intervertebral disk
Pubic symphysis
Sites of insertion of tendon and ligament onto bone
Synovial joints are limited by __________
Connective tissue capsule
Layers of synovial joints
- Outer layer of DICT
- Inner layer, called synovial membrane
- LCT = Loose Connective Tissue
- Fenestrated blood vessels
- Synovial cells
Role of synovial fluid
Reduces friction between articular cartilage covering opposing articular surfaces
The synovial membrane encloses the ____________, which contains ____________
Synovial cavity
Synovial fluid
Two disease causes by the weaking or degradation of the articular cartilage
Osteoarthritis
Rheumatiod arthritis
Articular cartilage is almost typical hyaline cartilage but it’s missing a few things, like:
- Not lined by epithelium
- no perichondrium
- no endochondral ossification
What’s unique about articular cartilage?
They have a unique collagen fiber organization in the form of overlapping arches, which makes them able to sustain mechanical stress in joint surfaces
Osteoarthritis
- Characterized by a loss of articular cartilage
- Cause is unknown
- Affects 50% of people 65 and older
- In some forms, calcified deposits form in joints
- Protease secretion is upregulated by chondrocytes
- Treatments include anti-inflammatory agents, joint replacement
Rheumatoid Arthritis
- Autoimmune disease
- Inflammation of synovial membrane leads to erosion of articular cartilage and destruction of subjacent bone
- (A) Key cytokines in driving inflammation: tumor necrosis factor-α (TNF-α), interleuking-1 (IL-1), and IL-6
- Can be detected in synovial fluid
- (B) Cytokines cells to release cartilage and bone-destroying matrix enzymes
- (C) Secretion of collagenase and other enzymes by monocytes and macrophages
What is Pannus?
- Pannus = inflamed, proliferating synovium characteristic of rheumatoid arthritis
- Pannus invades cartilage and eventually bone surface à destruction of cartilage and bone, which leds to destruction of joint
- Treatment: neutralization of proinflammatory cytokines by soluble receptors or monoclonal antibodies
highly vascularized and metabolically very active. Cartilage or bone?
Bone
What is unique about EMC of bone compared to cartilage?
Impregenated with calcium and phosphate salts
Function of Bone
Resevior for calcium and phosphate ions
Movement and posture by provide attachment for muscles and tendons
Support and protection for body and its organs
Compact bone (dense bone)
- Appears as solid mass; external layer of bone
- Arranged in osteons
- Lamellae are found around periphery and between osteons
- Central canals connected to each other by perforating canals
Spongy bone also known as _______.
Characteristics
Trabecular or cancellous bone
- Consists of network of bony spicules or trabeculae delimiting spaces occupied by bone marrow
- No osteons; arranged in trabeculae
- Major type of tissue in short, flat, irregular bones
- Much lighter than compact bone
- Support red bone marrow
Major type of tissue in short, flat, irregular bones
Spongy bone
What are trabecullae and what role do they play?
Bands or columns of connective tissue in spongy bone. They provide structure.
Which bones in our body are long bones?
Clavicle
Humerus
Radius
Ulna
Metacarpus
Phalanges
Femur
Tibia
Fibula
Metatarsus
Components of Long Bone
•Shaft or diaphysis (Medial)
- Consists of compact bone forming a hollow cylinder with central marrow space (medulla or marrow/medullary cavity)
•Epiphysis (Distal)
- consists of spongy bone covered by thin layer of compact bone
•Articular surfaces, at end of long bones, covered with hyaline cartilage (articular cartilage)
Most bones are surrounded by _____________. What are the exceptions?
Periosteum
•Exceptions: articular surfaces and insertion sites of tendons and ligaments
What is osteogenic potential? What components of long bone have this capacity?
Bone regeneration capacity
Periosteum; Endosteum
Periosteum is made up of ________
Specialized connective tissue
Marrow cavity of diaphysis and spaces within spongy bone are lined by __________
endosteum
Endosteum is made up of
Squamous cells and connective tissue fibers. It extends into all bone cavities.
*When endosteal cells become activated they can function as osteoblasts
Layers of periosteum
Outer fibrous layer
- Rich in blood vessels and thick anchoring collagen fibers, called Sharpey’s fibers, that penetrate outer circumferential lamallae
Inner Osteogenic layer
What are Sharpey’s fibers?
They are think anchoring collagen fibers, found in the periosteum of long bones, that penetrate outer circumferential lamellae and are also used to attach muscle to bone by merging with fibrous periosteum and underlying bone.
Epiphyses are separated from diaphysis by a cartilaginous ______________, connected to the diaphysis by _____________
epiphyseal plate; spongy bone
What is a metaphysis?
Zone of spongy bone that connects epiphysis and diaphysis
Whta two components are responsible for the increase in length of long bone?
Epiphyseal plate
Metaphysis
What are microscopic components of bone?
Lamellar bone
- Spongy bone
- Compact bone
Woven bone
Lamellar bone
- Typical of mature bone
- With regular alignment of collagen fibers
- Mechanical strong
- Formed slowly
Woven bone
- In developing bone
- Irregular alignment of collagen fibers
- Mechanically weak
- Formed rapidly and replaced by lamellar bone
- Also produced during repair of bone fractures
What is found at the center of each osteon?
Haversian canal
What are the two orientations of vascular channels in compact bone, with regard to lamellar structures?
- Longitudinal capillaries running in center of osteon within Haversian canal
- Haversian canals are connected with one another by transverse or oblique canals known as Volkmann’s canals (containing blood vessels from the marrow and some from the periosteum)
.Haversian canals are connected with one another by transverse or oblique canals known as ____________
Volkmann’s canals
Components of Bone Matrix
Inorganic (65%) components
- 85% deposits of calcium phosphate [Ca3(PO4)2]
- 15% calcium carbonate (CaCO3)
Organic (35%) components
- 90% collagen type 1 fibers;
- 10% proteoglycans
- non-collagenous proteins
Components of proteoglycan
Chondriotin sulfate
Keratan sulfate
Hyaluronic acid
What are the two different lineages of actively growing bone?
Osteoblast lineage
- Derived from mesenchyme
- Gives rise to oseogenic cells, Osteoblasts, and osteocytes
Osteoclasts
- Derived from monocyte-machrophage lineage in the bone marrow
- Gives rise to osetoclasts
Osteoblasts
- Epithelial-like cells with cuboidal or columnar shapes
- Form a monolayer covering all sites of active bone formation
- Are highly polarized cells: deposit osteoid (nonmineralized organic matrix of the bone) along the osteoblast-bone interface
- Initiate and control subsequent mineralization of osteoid
Steps of Bone mineralization
- Osteoblasts extrude matrix vesicles into their environment
- These vesicles release crystals of hydroxypatite that serve as “seed crystals” for mineralization
3.
Role of alkaline phosphatase
An enzyme that degrades a calcification inhibitor, pyrophosphate
Osteocytes
Highly branched cells with their body occupying lacunae (small spaces between lamellae)
•When bone formation is completed, osteoblasts flatten out and transform into _____________
osteocytes
____________ course through lamallae and interconnect neighboring lacunae.
Canaliculi
Adjacent cell processes, found within canliculi (small channels), are connected by __________
Gap junctions
How do nutrients travel in osteocytes?
•Nutrients diffuse from blood vessel within Haversian canal through canaliculi into lacunae
Dense network of osteocytes depends on:
- Intracellular communication across gap junctions
- Mobilization of nutrients and signaling molecules along the extracellular environment facilitated by canaliculi running from lacuna to lacuna
Differentiation of osteoblasts involve which 2 transcription factors. What are the roles of each?
Sp7
- Expression induces mesechymal cells to differentiate into osteoblasts, and subsequently osteocytes
- Inhibits chondrocyte differentation
Runx2
- Scaffold for regulatory factors involved in skeletal gene expression
Runx2 is also known as ______
Cbfa1
Sp7 is also known as ________
Osterix
•Several members of the _________ family and ___________ can regulate the embryonic development and differentiation of the osteoblast
BMP; transforming growth factor-beta (TGF-β)
A pluripotent mesechymal cell can differentiate into which cells?
Osteoblasts
Muscle cells
Adipocytes
Firbroblasts
Chondroblasts
___________induces expression of Runx2/Cbfa1
BMP7
Cleidocranial dysplasia (CCD) symptoms
Hypoplastic clavicles
Delayed ossification of sutures of certain skull bones
Mutations in Runx2/Cbfa1 genes
Which cells of the bone play a huge role in bone remodeling and renewal?
Osteoclast
Osteoclast activity is regulated by which hormones?
Calcitonin
Vitamin D3
Mechanism for bone degradation
- αvβ3 integrin—F-actin—osteopontine complex organizes the sealing zone resulting in isolation of resorption space from extracellular space
- Protons , generated by carbonic anhydrase II (CAII) activity, are transported through H+-ATPases present in the ruffled membrane and an acidic environment (pH ~4.5) mobilizes bone minerals
The cytoplasmic electroneutrality of osteoclast is maintained by ________
Cl-/HCO3- exhange
___________ is secreted by exocytosis and degrades bone organic matrix (collagen & non-collagen proteins) following solubilization of minerals by acidification
Cathepsin K
•How do osteoclast get to bone region to resorb?
- Fatigued bones display microscopic regions of damage called microcracks
- Osteocytes near microcracks undergo apoptosis
- RANKL induces osteoclast activity by binding to its receptor
- Osteoclast activity is stimulated, followed by osteoblast activity
- Reabsorbs damaged bone and replaces it with new healthy bone
Osteoclastogenesis
- = osteoclast differentiation = process regulated by osteoblasts and stromal cells of bone marrow
- Is triggered by two relevant molecules produced by osteoblast
- (1) macrophage colony-stimulating factor (M-CSF)
- (2) Receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)
Osteopetrosis
- Rare, autosomal dominant or recessive
- In humans, osteopetrosis is characterized by high-density bone due to absent osteoclastic activity
- In long bones, this condition leads to occlusion of marrow spaces and to anemia
- Osteosclerosis (form of osteopetrosis): increase in bone mass due to increase in osteoblastic activity
Osteoporosis
- = Loss of bone mass leading to bone fragility and susceptibility to fractures
- Reabsorbed old bone >> formed new bone
- Due to increased number of osteoclasts
- Major factor is deficiency of sex steroid estrogen (e.g., postmenopausal woman)
- Estrogen stimulates production of osteoprotegerin
- Accelerated turnover state can be reversed by estrogen therapy and calcium and vitamin D supplementation
- Also observed in men
- Usually no symptoms until bone fractures
Osteomalacia
Disease characterized by progressive softening and bending of bones
- Softening because of defect in mineralization of osteoid
- Can result from
- Deficiency in vitamin D (for example intestinal malabsorption) or
- Heritable disorder of vitamin D activation (e.g., renal 1α-hydroxylase deficiency in which calciferol is not converted to the active form of vitamin D, calcitriol)
