Congenital Disorders of Bone and Cartilage

Question 1

Functions of Bone

Answer 1

Mechanical Support Transmission of Force Protect the Viscera Mineral Homeostasis Acid-Base balance Niche for production of blood cells

Question 2

Intramembranous Ossification

Answer 2

Bone laid down directly in embryonic connective tissue or mesnechyme….all bones of the head and the clavicle.

Question 3

Endochondral Ossification

Answer 3

Bone tissues replaces preexisting hyaline cartilage(the template for future bone)

Question 4

Woven Bone

Answer 4

Immature bone (or pathologic) seen after a fracture or in development. randomly oriented and more osteocytes per unit volume. flexible, weak, high turnover rate

Question 5

Lamellar Bone

Answer 5

Remodeled and organized bone. Stronger but less flexible.

Question 6

Steps in Endochondral Ossification

Answer 6

1. Mesenchymal condensation 2. Type 2 Collagen synthesis and chondrocyte proliferation 3. Type 10 collagen synthesis and chondrocyte hypertrophy 4. Type 1 collagen formation and matrix mineralization. Nutrient artery brings pre-osteoblastic cells.

Question 7

FGF Receptor 3 (FGFr3) function and associated dysfunction

Answer 7

Functions to shut off chondrocyte growth. Gain of function mutation causes short stature due to decreased chondrocyte differentiation and proliferation

Question 8

Cortical Bone vs Trabecular Bone

Answer 8

Cortical- Long bone shafts. Concentric layers of mineralized hardened colagen. Resistant to bending and torsion. Trabecular- Sxial skeleton and ends of long bones. Rigid but Spongy. Large surface area due to trabecular meshwork

Question 9

What is Osteopontin

Answer 9

It is unique to bone and serum measures indicate osteoblast activity

Question 10

What type of collagen is found in osteoid?

Answer 10

Type 1 collagen

Question 11

Osteoblast

Answer 11

Derived from mesenchymal progenitors Produces collagen and other matrix proteins

Question 12

Osteoclast

Answer 12

Derived from hematopoietic progenitors Resorb Bone Multinucleated and mobile

Question 13

Osteocytes and Lining cells

Answer 13

Mature osteoblasts Line bone surface or embed in matrix Homeostatic function

Question 14

What two signals are required for Osteoclast Maturation

Answer 14

RANKL (Formation) M-CSF (Growth, Survival, Differentiation)

Question 15

How do osteoclasts function?

Answer 15

Creates a sealing zone….then Cathespin K digests the proteinaceuos matrix

Question 16

Cathepsin K

Answer 16

digests the bone. produced by osteoclasts

Question 17

Dysostosis

Answer 17

Localized problem in the migration or condensation of mesenchyme. Absence of a bone or digit (Aplasia) Extra bone or Digit Abnormal bone fusion (syndactyly)

Question 18

Dysplasia

Answer 18

Abnormal growth/disorganization of bone or cartilage

Question 19

Camptomelic Dysplasia

Answer 19

Sox 9 (allows chondrocytes to differentiate) mutation that causes a short-limbed dwarf. neonatal death. bowed long bones.

Question 20

Runx2 function and disorder

Answer 20

regulates commitment to osteoblast lineage. No runx2 = cartilage skeleton w/o bone Cleidocranial Dysplasia

Question 21

GDF5

Answer 21

Promotes chondrogenesis. Lack of GDF5 causes shortening of the appendicular skeleton. Loss of some joints. (Bradydactyly or chondrodysplasia)

Question 22

Achondroplasia

Answer 22

Most common type of short limb dwarfism Activating mutation in FGFr3 Paternal mutation related to paternal age. decreased endochondral ossification

Question 23

Structure of Type 1 Collagen

Answer 23

Trimer of two pro-alpha 1 chains (chromosome 17) one pro-alpha 2 chain (chromosome 7)

Question 24

Osteogenesis Imperfecta Type 2

Answer 24

Perinatal Lethal. Most sever form Skeletal deformity with numerous fractures

Question 25

Ostegenesis Imperfecta Type 1

Answer 25

Mildest from of OI. Autosomal Dominant Blue Sclera (thin sclera so veins show through) Hearing Loss

Question 26

Osteopetrosis

Answer 26

increased bone mass and mineralization Decreased Osteoclast function acidification defect. associated with RankL defect “Ehrlenmeyer Flask” deformity