BD: Biochemistry of Bone Formation Flashcards
- What are the four phases of skeletal development?
a. 1. Migration
b. 2. Interaction
c. 3. Mesenchymal condensation
d. 4. Differentiation
- What are the two types of bone formation?
a. 1. Endochondral
b. 2. Intramembranous
- Which bone formation type is indirect?
Endochondral
What occurs in endochondral bone formation?
The bone starts as cartilage
What bones are usually endochondral?
Bones that bear weight
What bone formation is direct?
Intramembranous
- Why is it intramembranous bone formation direct?
Because the mesenchymal cells become osteoblasts with no cartilage intermediate
- Where is intramembranous bone formation restricted at?
a. It is restricted to the cranial vault and facial bones
- What molecules attract hypertrophic chondrocytes to blood vessels to invade?
VEGF
- When does growth plate fusion occur?
Age 14-20
- When do secondary ossification centers appear?
a. Around the time of birth
- What is the first type of bone produced?
a. Woven bone/Primary bone
- When is woven bone most often found?
During fractures
What is woven immature bone replaced with?
Lamellar bone
What can lamellar bone be classified into?
- Compact bone
- Cancellous bone
What are the three main bone cell types?
- Osteoclasts
- Osteoblasts
- Osteocytes
What is unique about osteoblasts, chondroblasts, myoblasts, and adipocytes?
They all originate from a mesenchymal progenitor
What type of collagen is produced from osteoblasts?
Type 1
What are the two transcription factors used in osteoblasts?
RUNX2
Osterix
What are the extracellular matrix proteins used in osteoblasts?
Type 1 collagen
Osteopontin
Osteocalcin
Bone sialoprotein
What does RUNX2 and Osterix do?
RUNX2
i. Allows mesenchyme to mature into immature osteoblasts Osterix
i. Allows immature osteoblasts to mature into mature osteoblasts
What molecules inhibit these steps?
B-catenin
What is the master transcription factor for osteoblasts?
RUNX2
- In humans, if RUNX2 is mutated what occurs?
a. Cleidocranial dysplasia
Is cleidocranial dysplasia an autosomal dominant or haploinsufficient mutation of
RUNX2?
Both
What molecules does osterix control?
Type 1 collagen
Osteocalcin
Osteopontin
What do mutations in osterix cause in humans?
Osteogenesis imperfecta type 12
- What two key molecules regulate osteoblast differentiation besides RUNX2 and Osterix?
- BMPS
- WNT/B-Catenin
What do BMPs do?
Maintain adult bone homeostasis
What is FOP (Fibrodysplasia Ossificans Progressiva)?
Heterotopic bone formation that results in a stone man appearance due to a BMP
type 1 mutation
What does this mean in regards to FOP?
Everytime soft tissue damage occurs, bone take its place
What is the high bone mass phenotype caused by?
Mutations of LRP5
What does the LRP5 mutations affect?
Wnt/B-Catenin signaling
What does inactivating mutations of LRP5 cause?
a. Low bone mass
- What initiates the first phase of mineralization?
a. Matrix vesicle secretion
- What initiates the second phase of mineralization?
a. Propagation of mineralized collagen fibers
- What enzyme is highly expressed in osteoblasts and odontoblasts?
a. Alkaline phosphatase (AP)
- What does AP do?
a. Hydrolyzes pyrophosphate which leads to mineralization
- Why is hydrolyzing pyrophosphate important in the mineralization process?
a. Because pyrophosphate is an inhibitor of mineralization
- What disorder is associated with mutations in alkaline phosphate?
a. Hypophosphatasia
- What gene causes this?
a. TNSALP
- Is there a master transcriptional gene identified for osteocytes yet?
No
- What gene controls the transcription factors for osteocytes?
Mef2c
- What are the potential functions of osteocytes?
a. Mechanosensors
b. Bone resorption and bone formation
c. Regulation of mineralization
d. Mineral homeostasis
- What gene is used by osteocytes to regulate osteoblasts?
Sclerostin
- What cells express sclerostin?
a. Osteocytes
b. Cementocytes c. Odontoblasts
- How does sclerostin negative regulate bone formation?
a. Through the antagonistic affect of Wnt/Beta-catenin signaling
- What do sclerostin mutations cause?
a. Vanbuchems disease
- What is Van Buchems disease?
a. Bone mass increases in craniofacial skeleton (Crimson chin disease)
- What genes do osteocytes express that are important in phosphate homeostasis?
a. FGF23
b. DMP1
c. PHEX