1
Q
What kind of tissue is bone?
A
connective tissue
2
Q
Bone consists of
A
cells, fibers and extracellular matrix mater
3
Q
Extracellular components of bone are
A
hard and calcified
4
Q
What is the ratio of ECM and bone cells?
A
ECM is more abundant than cells and contains lots of collagen
5
Q
ECM of bones are high in
A
collagen
6
Q
What is the function of bones?
A
- Support—bones form the framework-shape, alignment, and positioning
- Protection—protect the structures they enclose
- Movement—bones with joints function as levers that move
- Mineral storage reservoir for calcium, phosphorus,
- Hematopoiesis—blood cell formation
7
Q
______ and ______ of bone allows it to serve its supportive and protective functions
A
Rigidity
strength
8
Q
What are the types of bones?
A
A. Long bones
B. Short bones
C. Irregular bones
D. Flat bone
9
Q
Compact bone is
A
dense and used for support
10
Q
Spongy bone (cancellous) or trabecular bone forms
A
a calcified lattice
11
Q
_____ is the end of a long bone.
A
Epiphysis
12
Q
_______ is the site of bone growth
A
Epiphyseal plate
13
Q
____ is the shaft of along bone.
A
Diaphysis
14
Q
Diaphysis
A
- Main shaft of long bone
- Hollow, cylindrical shape and thick, compact bone
- Function is to provide strong support without cumbersome weigh
15
Q
Epiphysis
A
- Both ends of a long bone, made of cancellous bone filled with marrow
- Bulbous shape
- Function is to provide attachments for muscles and give stability to joint
16
Q
Articular cartilage
A
• Layer of hyaline cartilage that covers the articular surface of epiphyses
17
Q
Hyaline cartilage
A
Elastic cartilage,
Function is to cushion jolts and blows
18
Q
Periosteum
A
- Dense, white, fibrous membrane that covers bone
- Attaches tendons firmly to bones
- Contains cells that form and destroy bone
- Contains blood vessels important in growth and repair
- Contains blood vessels that send branches into bone
- Essential for bone cell survival and bone formation
19
Q
What does periosteum contain?
A
- Contains cells that form and destroy bone
- Contains blood vessels important in growth and repair
- Contains blood vessels that send branches into bone
20
Q
Endosteum
A
thin epithelial membrane that lines medullary cavity
21
Q
Medullary (or marrow) cavity
A
- Tubelike, hollow space in diaphysis
* Filled with yellow marrow in adult
22
Q
What are the layers of bones from superficial to deep?
A
Periosteum
Endosteum
Medullary (or marrow) cavity
23
Q
Short, flat, and irregular bone features
A
Inner portion is cancellous bone, covered on the outside with compact bone
Spaces inside cancellous bone of a few irregular and flat bones are filled with red marrow
Large amounts of red bone marrow are found in flat bones like those of the ribs, pelvis and skull
24
Q
Large amounts of red bone marrow are found in _____ like those of the ribs, pelvis and skull
A
flat bones
25
The Extracellular Matrix of Bone is made up of ________ and ______
an Organic and an Inorganic component
26
Inorganic salts
–The hardness of bone results from the deposition of
-->Hydroxyapatite—highly specialized chemical crystals of calcium and phosphate
–Found in the spaces between the collagen
–Also about 10% calcium carbonate
–Slender, needle-like crystals are oriented to most effectively resist stress and mechanical deformation–Magnesium and sodium are also found in bone
27
Hydroxyapatite
highly specialized chemical crystals of calcium and phosphate
28
Inorganic salts are found in
the spaces between the collagen
29
Organic matrix
secreted by bone cells (osteoblasts, derived from mesenchymal stem cells). They become imprisoned in the matrix
• Collagenous fibers and a mixture of protein and polysaccharides which forms a gelatinous material termed ground substance
• Ground substance is also important in bone growth, repair and remodelling as it acts as a medium for the diffusion of nutrients, oxygen and metabolic waste. This organic matrix combines with large amounts of crystallized minerals. Mostly calcium to give bone its rigidity
30
Collagenous fibers
Collagenous fibers and a mixture of protein and polysaccharides which forms a gelatinous material termed ground substance
31
Ground substance
Ground substance is also important in bone growth, repair and remodelling as it acts as a medium for the diffusion of nutrients, oxygen and metabolic waste.
This organic matrix combines with large amounts of crystallized minerals. Mostly calcium to give bone its rigidity
32
Four types of structures make up each osteon:
* Lamella
* Lacunae
* Canaliculi
* Haversian canal
33
Lamella
concentric rings that are , islands of calcified matrix. Altered by growth. Think of Tree rings
34
Lacunae
small spaces containing tissue fluid in which bone cells (osteocytes) are located between hard layers of the lamella
35
Canaliculi
ultra small canals radiating from the osteocytes and connecting them to each other and to the Haversian canal (part of network that allows excretion and absorbtion of nutrients)
36
Haversian canal
extends lengthwise through the center of each osteon and contains blood vessels and lymphatic vessels
37
Structure of the Cancellous Bones
–There are no osteons in cancellous bone; instead, it has trabeculae-needle like bony spicules
–Nutrients are delivered and waste products removed by diffusion through tiny canaliculi(canals radiating from bone cells)
–Bony spicules are arranged along lines of stress, enhancing the bone’s strength
38
Difference in structure between cancellous bone and compact bone
- Cancellous bone between compact bone (common in flat bones)
- Cancellous bone found on the inner surface of long bone
39
What are the 4 types of bone cells?
Osteogenic cells
Osteoblasts
Osteocytes
Osteoclasts
40
Osteogenic cells
differentiate and develop into osteoblasts
41
Osteoblasts
- synthesize and secrete the collagen in matrix
- deposit calcium as they create new bone matrix
- Bring about the formation of new bone
- Facilitate the deposition and exchange of calcium
- Determine osteoclast formation through the RANKL receptor ligand system
42
Osteocytes
Osteoblasts can become trapped in the matrix when it calcifies (mature bone cells)
43
Osteoclasts
- stem from macrophages (not osteogenic cells)
- break down bone matrix during bone resorption
- Responsible for the active erosion of bone minerals
- Formed by the fusion of several precursor cells multinucleated
- Develop from stem cells in bone marrow
- Attach to bone surface by integrins
- Contain large numbers of mitochondria (energy) and lysosomes (enzymes to break down macromolecules)
- Bring about the resorption of bone by secretion of collagenase, Matrix mettaloproteinases(MMPs) and the secretion of lactic and citric acids
- MMPS destroy ECM such as collagen
44
MMPS destroy ______
ECM such as collagen
45
Osteoclasts develop from ______
stem cells in bone marrow
46
Osteoclasts attach to bone surface by ____
integrins
47
Osteoclasts contain _____
arge numbers of mitochondria (energy) and lysosomes (enzymes to break down macromolecules)
48
Osteoclasts bring about the resorption of bone by secretion of ______
```
collagenase,
Matrix mettaloproteinases(MMPs) and the secretion of lactic and citric acids
```
49
True/False
bone surfaces are covered with layer of cells mostly made of osteoclasts (bone reabsorbing), and less osteoblasts (bone building)
False
bone surfaces are covered with layer of cells mostly made of osteoblasts (bone building), and less osteoclasts (bone re-absorbing cells)
50
What is RANKL?
RANKL is on surface on osteoblast and bind its receptor RANK on osteoclast precursor cells.
This interaction leads to the differentiation of osteoclast precursor cells and the activation of osteoclasts to resorb bone
51
Stimulators of RANKL process are ______
Parathyroid hormone (released from thyroid to trigger release of Calcium)
52
Inhibitors of RANKL are ______
Inhibitors are estrogen acting vis osteoprotegrin
53
How do skeletal bones help the calcium homeostasis in the body?
Maintains and modulates blood calcium levels
- Calcium is mobilized and moves into and out of blood during bone remodelling
- During bone formation ca removed by Ob deposited in bone
- During breakdown of bone, osteoclasts release calcium into blood and increase circulating levels
- This process is controlled by : parathyroid hormone(parathyroid gland-posterior to the thyroid) calcitoninby the (thyroidgland) and by Vitamin D
54
What can affect Calcium Balance?
* Age, disease, diet, medications
* Children usually have a positive balance that allows bone to grow
* In adults input and output should be the same
* Post-menopausal women tend to have a negative calcium balance
* Dietary intake is variable so the body must be able to adapt to raised or reduced levels
55
There are three major paths of calcium regulation:
- Parathyroid hormone
- Calcitonin
- Vitamin D
56
Parathyroid hormone is released when ________
plasma Ca+ concentration is low
57
How does parathyroid hormone work in terms of calcium regulation?
Mobilizes calcium from bone
Enhances renal reabsorption of calcium
Stimulates release of Calcitriol
58
What does calcitriol do?
Calcitriol increases intestinal calcium absorption
59
Calcium in the body is divided into three pools
1. Extracellular calcium (0.1% of total)
2. Intracellular calcium (0.9% of total)
3. Calcium in bone matrix (99% of total)
60
How does calcitonin effect Ca+ homeostasis?
acts in opposite manner to PTH
61
When is calcitonin produced?
Produced in response to high blood calcium levels
| Calcitonin(released when plasma Ca2+is high)
62
How does calcitonin function?
Decreases bone resorption
| Increases renal calcium excretion
63
Where does Vitamin D (calcitriol) come from?
* Vitamin D (Calcitriol) is absorbed by the small intestine as part of the diet
* OR, is synthesized from exposure of skin to UV light converts 7-dehydrocholesterol to cholecalciferol—in the skin to a precursor of vitamin D
64
How is Vitamin D (calcitriol) is produced from skin exposure to UV light?
converts
7-dehydrocholesterol --> cholecalciferol
—in the skin to a precursor of vitamin D
65
Actions of Vitamin D on calcium regulation:
– Increased calcium reabsorption in the proximal and distal convoluted tubules of the kidney
–Vitamin D stimulates osteoblastactivity to increase bone mass and calcification
–In the intestine increases the synthesis of calcium binding proteins on intestinal cells
–Disorders of Vitamin D can cause weak bones (rickets in children or osteomalaciain adults)
66
Vitamin D stimulates
osteoblastactivity to increase bone mass and calcification
67
Disorders of Vitamin D can cause
weak bones (rickets in children or osteomalaciain adults)
68
Calcification by
laying down of calcium salts (calcium and phosphorous)
69
There are two mechanisms for bone formations
1. Intramebranous
some flat bones, no cartilage
2. Endochondral
cartilage, vascular, long and flat bones
70
Intramebranous bone formation occurs when
occurs when fibrous membranes are replaced by bone tissue (less common)
71
Where and how does intramebranous bone formation happen?
Flat bones, like the bones of the skull, sternum, and clavicle
–does not begin with a cartilage model.
–Instead, dense areas of mesenchymal cells (multipotent stem cells) differentiate and begin to lay down bone around themselves, forming early spicules.
72
intramebranous bone formation does not begin with a cartilage model. Instead _______
dense areas of mesenchymal cells (multipotent stem cells) differentiate and begin to lay down bone around themselves, forming early spicules.
73
in intramebranous bone formation dense areas of __________ (multipotent stem cells) differentiate and begin to lay down bone around themselves, forming early _______.
mesenchymal cells
| spicules
74
What are the 2 major steps of intramebranous bone formation
1. Spongy bone tissue begins to develop at sites within the membranes called centers of ossification.
2. Red bone marrow forms within the spongy bone tissue, followed by the formation of compact bone on the outside
75
Intramembranous bone development occurs within a
connective tissue membrane
76
Intramembranous bone development begins with
migration of mesenchymal stem cell which to the site of bone formation and differentiate into osteoblast
77
How do osteoblasts act in intramembranous bone development
Osteoblasts are clustered together in centers of ossification
Osteoblasts secrete matrix material and collagenous fibrils (ground substance or osteod)
78
How does mineralization occur in intramembranous bone formation
(calcium and phosphate) the organic strands once mineralized are called trabecula (little beam)
79
Endochondral bone development
Most bones begin as a cartilage model, with bone formation spreading essentially from the center to the end
80
How do mesenchymal cells act in endochondral bone formation?
Mesenchymal stem cell migrate to the site of eventual bone development
81
in endochondrial bone formation mesenchymal cells are induced to become ____
These cell are induced to become chondrocytes (cartilage cells)
82
In endochondrial bone formation chondrocytes differentiate into _____
very dense avascular mass
83
Cartilage forms in the shape of _____
the bone
84
Endochonral ossification
The cartilage is surrounded by periosteum (envelope of connective tissue) develops and enlarges
85
In endochondral ossification, the cartilage is surrounded by ________ (envelope of connective tissue) develops and enlarges
periosteum
86
In endochondral ossification, osteoblasts which differentiate from the __________ produce a ______
inner surface of the periosteum
| collar of bone
87
When does primary ossification site occurs in endochondral ossification?
Osteoblasts which differentiate from the inner surface of the periosteum produce a collar of bone
88
Blood vessel enters the cartilage at the midpoint of the _______
diaphysis
89
Bone grows in length as endochondral ossification progresses from the _____ toward ________
diaphysis
| each epiphysis
90
Bones elongate as __________
chondrocytes in cartilage of epiphyseal plate divide
91
epiphyseal plate divisions –produce new cartilage within the _________
epiphyseal plate bordering the epiphyses.
92
At the other end of the epiphyseal plate, bordering the diaphysis, older cartilage is broken down by __________
invading osteoclasts and eventually replaced by the expanding medullary cavity.
93
Epiphyseal plate is composed of four layer
- Zone of proliferation
- Zone of hypertrophy
- Zone of calcification
- Ossification zone
94
Zone of proliferation
cartilage cells (chondrocytes) undergoing active mitosis, causing the layer to thicken and the plate to increase in length
95
Zone of hypertrophy
older, enlarged cells undergoing degenerative changes associated with calcium deposition
96
Zone of calcification
dead or dying cartilage cells undergoing rapid calcification
97
Ossification zone
matrix undergoes calcification
98
When do Epiphyseal plate fuse?
around puberty
99
Where does epiphyseal plate remain until bone growth in length is complete?
Epiphyseal plate remains between diaphysis and each epiphysis until bone growth in length is complete
100
When does closing of the bone happen?
–Digits close early
| –Arm, leg, and pelvis bones close later
101
Why does closing happen in different times in women and men?
due to sex hormones
102
Endochondral ossification step-by-step
1. Chondrocytes at the center of the growing cartilage model enlarge and then die as the matrix calcifies.
2. Newly derived osteoblasts cover the shaft of the cartilage in a thin layer of bone.
3. Blood vessels penetrate the cartilage. New osteoblasts form a primary ossification center.
4. The bone of the shaft thickens, and the cartilage near each epiphysis is replaced by shafts of bone.
5. Blood vessels invade the epiphyses and osteoblasts form secondary centers of ossification.
103
How do bones grow in diameter?
Bones grow in diameter by the combined action of osteoclasts and osteoblast
104
How do osteoblasts and osteoclasts act in bone growth in diameter?
* Osteoclasts enlarge the diameter of the medullary cavity
| * Osteoblasts from the periosteum build new bone around the outside of the bon
105
What is appositional bone growth and what happens in terms of osteoblast and osteoclast action?
• Enlargement in the diameter of bones occurs as it is growing in length
• Periosteum cells develop into osteoblasts
–Produce more matrix on the outer surface of the bone
• Osteoclasts erode the inner surface
–Enlarging the marrow cavity
106
What are the symptoms of osteoporosis?
• symptoms include fractures of the vertebrae, wrists or hips, lower back pain, neck pain, bone pain or tenderness, loss of height over time, or stooped posture.
107
What are the treatments for osteoporosis?
* Use of drugs such, raloxifene, and calcitonin or through estrogen replacement therapy
* Another recommended treatment for osteoporosis is exercise. Studies show that exercise can cause an increase in bone density
108
What is the role of estrogen in bone formation and resorption? Explain the pathway
* Estrogen acts on osteoblast to stimulates the production of TGF-beta,
* TGF-βcauses the osteoblast cells to make osteoprotegerin (OPG)
* OPG binds to RANKL and prevents it from binding to the RANK receptors on the preosteoclasts. This prevents them from becoming osteoclasts and thus limits bone resorption.
* When there are low levels of estrogen, the levels of OPG decline, leaving RANKL to bind to RANK receptor and allowing differentiation of osteoclasts to proceed and bone resorption increases
109
Bone remodelling in adults
–Osteocytes in lacunae continuously remove and replace surrounding calcium salts
–Maintain surrounding matrix
–Osteoblasts and osteoclasts remain active
–Remodelling bone, especially spongy bone
110
Bone remodelling in young adults
–Remodeling is so rapid that about one-fifth of the skeletal mass is replaced each year
111
Linear growth of long bones occurs at specialized regions called ________, located at each end of the bone shaft
epiphyseal plates
112
The side of the plate closer to the end (epiphysis) of the bone contains continuously dividing columns of ________, collagen-producing cells of cartilage
chondrocytes
113
What are the hormones that affect the bone growth?
The growth spurt of adolescent boys used to be attributed solely to increased androgen production but it now appears that estrogens play a significant role in pubertal bone growth in both sexes.
114
The central region of the osteoclast secretes __
hydrochloric acid with the aid of carbonic anhydrase and an H+-ATPase. Osteoclasts also secrete protease enzymes that work at low pH. e combination of acid and enzymes dissolves the calci ed hydroxyapatite matrix and its collagen support. Ca2 + from hydroxyapatite becomes part of the ionized Ca2 + pool and can enter the blood.
115
What is the importance of Ca2+ in the body?
1. Ca2+ is an important signal molecule.
2. Ca2+ is part of the intercellular cement that holds cells together at tight junctions.
3. Ca2+ is a cofactor in the coagulation cascade.
4. Plasma Ca2+ concentrations affect the excitability of neurons.
116
Extracellular matrix Ca2++ function
• Cacified matrix of bone and teeth
117
Extracellular fluid Ca2+
* Neurotransmitter release at synapse
* Role in myocardial and smooth muscle contraction
* Cofactor in coagulation cascade
* “Cement” for tight junctions
* Influences excitability of neurons
118
Intracellular Ca2+
* Muscle contraction
| * Signal in second messenger pathways
119
When is PTH released? and What happens when PTH is released?
The stimulus for PTH release is a decrease in plasma Ca2+, monitored by a cell membrane Ca2+-sensing receptor (CaSR). The CaSR, a G protein–coupled receptor, was the first membrane receptor identified whose ligand was an ion rather than an organic molecule.
PTH acts on bone, kidney, and intestine to increase plasma Ca2 + concentrations. Increased plasma Ca2 + acts as negative feedback and shuts off PTH secretion.
120
Parathyroid hormone raises plasma Ca2 + in three ways:
1. PTH mobilizes calcium from bone.
osteoclasts do not have PTH receptors instead, PTH effects are mediated by a collection of paracrines, including osteoprotegerin (OPG) and an osteoclast differentiation factor called RANKL.
2. PTH enhances renal reabsorption of calcium.
regulated Ca2 + reabsorption takes place in the distal nephron. PTH simultaneously enhances renal excretion of phosphate by reducing its reabsorption. The opposing effects of PTH on calcium and phosphate are needed to keep their combined concentrations below a critical level. If the concentrations exceed that level, calcium phosphate crystals form and precipitate out of solution. High concentrations of calcium phosphate in the urine are one cause of kidney stones.
3. PTH indirectly increases intestinal absorption of calcium through its influence on vitamin D3
121
Calcitriol is vitamin ____
D3
122
3 hormones that are involved in calcium regulation
PTH
Calcitriol
Calcitonin
123
Calcitonin is released when _____
plasma Ca2+ increases
124
What is Paget’s disease
Calcitonin has been used medically to treat patients with Paget’s disease, a genetically linked condition in which osteoclasts are overactive and bone is weakened by resorption
125
What is an alternative for HRT?
estrogen therapy alone increases the risk of endome- trial and possibly other cancers, and some studies suggest that combined estrogen/progesterone HRT might increase risk of heart attacks and strokes. A selective estrogen receptor modulator (SERM) called raloxifene has been used to treat osteoporosis.
126
The 4 types of bone cells
- osteogenic cells
- osteoblasts
- osteocytes
- osteoclasts
127
The layers of bone from superficial to deep
periosteum
endosteum
medullary/marrrow cavity
128
give examples of short, flat and irregular bones
ribs
pelvis
skull
129
The inner portion of short flat and irregular bones are ____ and covered with _____ on the outside
cancellous bone
| compact bone
130
osteoblasts are derived from
mesenchymal cells
131
True/False
| Osteons can be seen in cancellous bone
False
| instead, trabecular needle like structure bony SPICULES
132
Osteoclasts are attached to bone surface with ___
integrins
133
Oc resort bone by secretion of ____
collagenase
Matrix metalloproteinase (MMP)
lactic acid
citric acid
134
How does PTH regulate blood Ca+ levels
promotes OC activity
enhances renal resorption of calcium
stimulates calcitriol - increases intestinal absorption of calcium
135
How is calcitriol stimulated
by PTH
136
What is calcitriol's function in regulating the blood calcium levels
increases intestinal absorption of calcium
137
What is the role of calcitonin in regulation of blood calcium
lowers blood calcium levels and favours calcium storage in bone by decreasing bone resorption and renal excretion
138
Name 2 enzymes that play opposite roles in regulating the blood calcium
calcitonin and PTH
139
What is the role of vitamin D in regulation of blood calcium
deposits calcium in bone
| stimulates OB
140
How does vitamin D affect kidneys
increases Ca+ reabsorption in proximal and convoluted tubules in kidney
141
Disorder of vitamin D can cause
rickets in children
| osteomalacia in adults
142
What is development of bone called
Osteogenesis
143
What are the 2 mechanisms of bone formation?
1. intramembranous
| 2. Endochondral
144
What is the difference between intramembranous and endochondral bone formation?
intramembranous - no cartilage (flat bones)
| endochondral - cartilage (long bones)
145
What are the 2 major steps of intamembranous bone formation?
1. spongy bone tissue develops - centers of ossification
| 2. red bone marrow forms within spongy bone and compact bone forms on the outside
146
ground substance secreted by OB is also known as
collagenous fibrils
| osteod
147
mineralized strands are called
trabecula
148
In endochondral bone formation the mesenchymal stem cells are induced to become
chondrocytes
149
in endochondral bone formation the blood vessels enter the cartilage at ______
midpoint of the diaphysis
150
Bone grows in length as endochondral ossification progresses from ____ toward ___
diaphysis --> epiphysis
151
Epiphyseal plate is composed of 4 layers
zone of:
- poliferation
- hypertrophy
- calcification
- ossification
152
What are the treatments options for osteoporosis?
Raloxifene
Calcitonin
ERT
