Cartilage and Bone Flashcards
1
Q
What do cartilage and bone have in common? How can they be differentiated?
A
Both
Abundant extracellular matrix
Cells inhabit spaces called lacunae
Bone
Vascular
Calcification
Stiff
Cartilage
Avascular
Resists calcification
Flexible
2
Q
Undifferentiated cells that can differentiate into chondroblasts. What’s their significance?
A
Chondrogenic cells
They form the perichondirum
3
Q
Mature cells of cartilage
A
Chondrocytes
4
Q
How does avascular cartilage receive nutrients?
A
By diffusion through ECM
5
Q
What type of cells do chondrogenic cells differentiate into?
A
Chondroblasts
6
Q
Are chondroblast mature or immature?
A
Immature
7
Q
From where are chondroblast derived?
A
Mesenchymal cells
8
Q
Components of chondroblasts
A
Lipids
Glycogen
Well-developed rER
Golgi Appatatus
9
Q
What are the two types of cartilage growth? What are characteristics of each?
A
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
10
Q
Chondrogenesis pathway
A
- Chrondroblasts produce and deposit type II collagen fibers and ECM
- Chrondroblasts are separated and trapped within spaces in the matrix
11
Q
Each isogenous group is enveloped by a __________matrix and separated by a ___________ matrix.
A
Territorial; interterritorial
12
Q
3 types of cartilage. Characteristics of each.
A
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
13
Q
How do fetuses and adults differ in terms of hyaline cartilage?
A
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
14
Q
What is the role of the perichondrium? What is the exception?
A
Covers surface of hyaline cartilage, except articular cartilage
15
Q
Layers of perichondrium
A
- Outer fibrous layer: contains bundles of type I collagen and elastin
- Inner chondrogenic layer: formed by flat chondrogenic cells that can differentiate into chondroblasts
16
Q
Which type of cartilage cells are active? Which type are not?
A
Chondroblasts are active
Chondrocytes are not active
17
Q
Components of the ECM of hyaline cartilage
A
Aggrecan (proteoglycan)
- Chondroitin sulfate (GAG)
- Core proteins
- Link proteins that bind to hyaluronic acid
Collagen II fibers
18
Q
Role of aggrecan
A
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
19
Q
Where can elasic cartilage be found?
A
ONLY in auricle and epiglottis
20
Q
What differentiates elastic cartilage from hyaline cartilage?
A
Presence of elastic fibers
*Makes elastic cartilage very flexible and able to regain its original shape after deformation
21
Q
Which cartilage type allows for the connection to bone?
A
Fibrocartilage
22
Q
How does fibrocartilage differ from hyaline cartilage?
A
- ECM: type I collagen fibers, low concentration of proteoglycans and water
- Lacks perichondrium
23
Q
Intermediate between hyaline cartilage and dense connective tissue
A
Fibrocartilage
24
Q
What parts of the body contain fibrocartilage?
A
Forms part of intervertebral disk
Pubic symphysis
Sites of insertion of tendon and ligament onto bone
25
Synovial joints are limited by \_\_\_\_\_\_\_\_\_\_
Connective tissue capsule
26
Layers of synovial joints
* Outer layer of DICT
* Inner layer, called synovial membrane
* LCT = Loose Connective Tissue
* Fenestrated blood vessels
* Synovial cells
27
Role of synovial fluid
Reduces friction between articular cartilage covering opposing articular surfaces
28
The synovial membrane encloses the \_\_\_\_\_\_\_\_\_\_\_\_, which contains \_\_\_\_\_\_\_\_\_\_\_\_
Synovial cavity
Synovial fluid
29
Two disease causes by the weaking or degradation of the articular cartilage
Osteoarthritis
Rheumatiod arthritis
30
Articular cartilage is almost typical hyaline cartilage but it's missing a few things, like:
* Not lined by epithelium
* no perichondrium
* no endochondral ossification
31
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
32
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
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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
34
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
35
highly vascularized and metabolically very active. Cartilage or bone?
Bone
36
What is unique about EMC of bone compared to cartilage?
Impregenated with calcium and phosphate salts
37
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
38
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
39
Spongy bone also known as \_\_\_\_\_\_\_.
Characteristics
Trabecular or cancellous bone
## Footnote
* 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**
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Major type of tissue in short, flat, irregular bones
Spongy bone
41
What are trabecullae and what role do they play?
Bands or columns of connective tissue in spongy bone. They provide structure.
42
Which bones in our body are long bones?
Clavicle
Humerus
Radius
Ulna
Metacarpus
Phalanges
Femur
Tibia
Fibula
Metatarsus
43
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)
44
Most bones are surrounded by \_\_\_\_\_\_\_\_\_\_\_\_\_. What are the exceptions?
Periosteum
•Exceptions: articular surfaces and insertion sites of tendons and ligaments
45
What is osteogenic potential? What components of long bone have this capacity?
Bone regeneration capacity
Periosteum; Endosteum
46
Periosteum is made up of \_\_\_\_\_\_\_\_
Specialized connective tissue
47
Marrow cavity of diaphysis and spaces within spongy bone are lined by \_\_\_\_\_\_\_\_\_\_
endosteum
48
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**
49
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
50
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.
51
Epiphyses are separated from diaphysis by a cartilaginous \_\_\_\_\_\_\_\_\_\_\_\_\_\_, connected to the diaphysis by \_\_\_\_\_\_\_\_\_\_\_\_\_
epiphyseal plate; spongy bone
52
What is a metaphysis?
Zone of spongy bone that connects epiphysis and diaphysis
53
Whta two components are responsible for the increase in length of long bone?
Epiphyseal plate
Metaphysis
54
What are microscopic components of bone?
Lamellar bone
* Spongy bone
* Compact bone
Woven bone
55
Lamellar bone
* Typical of mature bone
* With regular alignment of collagen fibers
* Mechanical strong
* Formed slowly
56
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
57
What is found at the center of each osteon?
Haversian canal
58
What are the two orientations of vascular channels in compact bone, with regard to lamellar structures?
1. Longitudinal capillaries running in center of osteon within Haversian canal
2. 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)
59
.Haversian canals are connected with one another by transverse or oblique canals known as \_\_\_\_\_\_\_\_\_\_\_\_
Volkmann’s canals
60
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
61
Components of proteoglycan
Chondriotin sulfate
Keratan sulfate
Hyaluronic acid
62
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
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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
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Steps of Bone mineralization
1. Osteoblasts extrude matrix vesicles into their environment
2. These vesicles release crystals of hydroxypatite that serve as "seed crystals" for mineralization
3.
65
Role of alkaline phosphatase
An enzyme that degrades a calcification inhibitor, pyrophosphate
66
Osteocytes
Highly branched cells with their body occupying lacunae (small spaces between lamellae)
67
•When bone formation is completed, osteoblasts flatten out and transform into \_\_\_\_\_\_\_\_\_\_\_\_\_
osteocytes
68
\_\_\_\_\_\_\_\_\_\_\_\_ course through lamallae and interconnect neighboring lacunae.
Canaliculi
69
Adjacent cell processes, found within canliculi (small channels), are connected by \_\_\_\_\_\_\_\_\_\_
Gap junctions
70
How do nutrients travel in osteocytes?
•Nutrients diffuse from blood vessel within Haversian canal through canaliculi into lacunae
71
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
72
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
73
Runx2 is also known as \_\_\_\_\_\_
Cbfa1
74
Sp7 is also known as \_\_\_\_\_\_\_\_
Osterix
75
•Several members of the _________ family and ___________ can regulate the embryonic development and differentiation of the osteoblast
BMP; transforming growth factor-beta (TGF-β)
76
A pluripotent mesechymal cell can differentiate into which cells?
Osteoblasts
Muscle cells
Adipocytes
Firbroblasts
Chondroblasts
77
\_\_\_\_\_\_\_\_\_\_\_induces expression of Runx2/Cbfa1
BMP7
78
Cleidocranial dysplasia (CCD) symptoms
Hypoplastic clavicles
Delayed ossification of sutures of certain skull bones
Mutations in Runx2/Cbfa1 genes
79
Which cells of the bone play a huge role in bone remodeling and renewal?
Osteoclast
80
Osteoclast activity is regulated by which hormones?
Calcitonin
Vitamin D3
81
Mechanism for bone degradation
1. αvβ3 integrin—F-actin—osteopontine complex organizes the sealing zone resulting in isolation of resorption space from extracellular space
2. 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
82
The cytoplasmic electroneutrality of osteoclast is maintained by \_\_\_\_\_\_\_\_
Cl-/HCO3- exhange
83
\_\_\_\_\_\_\_\_\_\_\_ is secreted by exocytosis and degrades bone organic matrix (collagen & non-collagen proteins) following solubilization of minerals by acidification
Cathepsin K
84
•How do osteoclast get to bone region to resorb?
1. Fatigued bones display microscopic regions of damage called microcracks
2. Osteocytes near microcracks undergo apoptosis
3. RANKL induces osteoclast activity by binding to its receptor
4. Osteoclast activity is stimulated, followed by osteoblast activity
5. Reabsorbs damaged bone and replaces it with new healthy bone
85
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)
86
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
87
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
88
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)
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