Bone Flashcards
What are the three types of bone cells?
Osteoblasts
Osteocytes
Osteoclasts
What activates osteoclasts? What inhibits them?
PTH activates
Calcitonin inhibits
What is the name of the inorganic “stuff” of bone? What is it made of?
Hydroxyapatite
Ca2+ and Phosphorus
What is the organic stuff that makes up bone? What is it made of?
Osteoid
Type I collagen, proteoglycans, glycoproteins
What is the component of osteoid that promotes hydroxyapatite formation? What is the specific one that is bone-specific?
Glycoproteins promote hydroxyapatite formation
Osteocalcin is the bone specific glycoprotein that is not found in any other tissue.
Why is bone so hard?
Combined hydroxyapatite and collagen type I – both are needed
Compare bone and cartilage in respect to mineral, water, collagen, neuronal and vascular structures.
Bone: 70% mineral, 25% water, Collage Type I, Neuronal and vascular structures present
Hyaline cartilage: No minerals, 75% water, Collagen Type II, No neuronal and vascular structures
What are osteoblasts? And what are the known osteoblast-specific genes?
Osteoblasts are specialized fibroblasts
Cbfa-1: TF, bone master gene
Osteocalcin
Growth factors that induce osteoblast differentiation
Bone morphogenetic proteins (BMPs)
What do osteoblasts make?
Osteoid: type I collagen and glycoproteins
How is bone formation completed?
By osteocalcin-mediated deposition of Ca2+ within the osteoid
What happens if you do not have hydroxyapatite?
There is no weight-bearing
Where are osteocytes located?
They occupy the lacunae between layers – lamellae – of bone matrix
How many osteocytes per lacuna?
1
What is the function of osteocytes? How long do they live?
They maintain bone matrix
They live about 25 years
How do osteocytes communicate with one another??
Cytoplasmic processes penetrate the matrix where they join processes of other osteocytes via gap junctions
What do osteoclasts do?
They destroy/remodel bone matrix
How do they develop? Where are they located?
They are multinuclear and develop from macrophages that fuse together
They are located in hollow areas of matrix termed “Howship’s lacunae”
What part of the osteoclasts attaches to the ECM to promote bone resorption?
The ruffled border of the osteoclast
What hormones regulate osteoclasts and how?
Calcitonin = inhibits PTH = activates (lysosomes -- cathepsin K and H+ --> add to the microenvironment)
What are the connective tissues that outline bone called?
Periosteum and Endosteum
Where are each of the three types of bone cells located?
Osteoblasts are located mostly in the periosteum with smaller numbers in the endosteum
Osteocytes are within lacunae of the bony matrix between the periosteum and endosteum
Osteoclasts are mostly found attached to bony matrix on the endosteal side
What are the two types of bone that make up the inside and outside of bone?
Compact/cortical bone: dense, no cavitation, on the outside
Spongy/cancellous/trabecular bone: cavitation, on the inside
What are flat bones and where are they mostly located?
2 plates of compact bone surround diploe of spongy bone
What are the two parts of long bones?
Diaphysis (shaft): compact with spongy bone lining marrow
Epiphysis (ends): caps of compact bone around spongy bone
What is contained within an osteon?
An osteon is a cylinder with concentric lamellae, lamellae have lacunae that harbor osteocytes that inter-communicate by canaliculi
What does the innermost lamella surround?
The Haversian Canal
What are the two ways in which bone develops?
- intramembranous: osteoblasts deposit osteoid onto mesoderm
- endochondral: osteoblasts deposit osteoid onto cartilage
How does Endochondral bone develop?
Bone forms on hyaline cartilage
At the diaphysis: osteoblasts invade calcified cartilage, secrete osteoid –> ossification
At the epiphysis: same process but articular cartilage remains at ends of bone and epiphyseal plate cartilage remains for growth in length
How do long bones get long?
Sex steroid hormones –> pituitary –> growth hormone (GH; somatotropin) –> liver –> somatomedin (IGF-I) –> epiphyseal plate
What are the 4 different zones involved in long bone growth?
- zone of proliferation: induced by somatomedin (IGF-I)
- zone of hypertrophy: 20% of all fractures occur here because of hollowed out nature
- zone of calcification: calcified cartilage has collagen X not collagen II
- zone of ossification: eosinophilic due to deposition of collagen I by osteoblasts
What is involved in fracture repair?
Macrophages remove debris.
Chondroblasts secrete a callus of hyaline cartilage.
Osteoblasts replace cartilaginous callus with bony callus.
Primary bone (aka woven bone) is replaced by lamellar secondary bone.
How are some difficult to heal fractures repaired?
By grafting
Also in the pipeline: bone morphogenetic proteins (BMP-2 & BMP-7)
Adult stem cells (MSCs) –> Osteoblasts
Growth factors or cells implanted within biodegradable sponges made of collagen
How often do we get a new skeleton?
Every 10 years
What is osteoporosis? Osteoporosis?
Osteopetrosis: dense heavy bone; osteoclasts lack ruffled border
Osteoporosis: resorption by osteoclasts outpaces osteogenesis = hollow fragile bones
How can osteoporosis be prevented?
Dietary Ca2+, vitamin D, weight bearing exercises
Bone mineral density screening every 2-5 years
What are stromal cells?
They are in the bone marrow and are induced by PTH to secrete 3 factors that regulate osteoclasts.
What are the three factors that are released by stromal cells upon PTH stimulation?
M-CSF: macrophage colony-stimulating facture, induces macrophage proliferation
RANK-L: induces macrophage differentiation into osteoclasts
OPG: osteoprotegerin antagonizes RANK-L by binding its receptor
Osteoblasts
inhibited by…..
induced by….
Inhibited by leptin (obesity > risk for osteoporosis)
Induced by BMP
Osteoclasts
inhibited by…
induced by….
Inhibited by calcitonin, osteoprotegerin
Induced by RANK-L
What is the PTH paradox?
Both osteoblasts and osteoclasts are induced by PTH.
However, osteoblasts are stimulated with spike in PTH concentration while osteoclasts are stimulated by a constant level of PTH.
What types of drugs are there for osteoporosis?
Anabolic drugs = pro-osteoblast
PTH 1-34: spikes of PTH levels by injection that favor osteoblasts production.
Anti-resorptive drugs = anti-osteoclast
SERM, raloxifene
Bisphosphonates
Calcitonin
