BJST Flashcards
used as a specific marker of
osteoblast activity
Serum Osteoponin
type 1 collagen + smaller amounts of GAGs + other proteins (osteopontin or osteocalcin- for bone formation and mineralization)
Osteoid
primarily hydroxyapatite which give bone its hardness and serves as a repository for 99% of the calcium and 85% of the phosphorus
Minerals
Produced rapidly (during fetal development or
fracture repair
Always abnormal in adults, but its presence is not specific for any particular disease
Woven Bone
Supported by bony trabeculae interspersed with marrow, may be fatty (white) or hematopoietic (red)
Lamellar Bone
Located on the surface of the osteoid matrix
Synthesize, transport, and assemble matrix and regulate mineralization
Osteoblast
Connected by an intricate network of dendritic cytoplasmic processes through tunnels (canaliculi)
Controls calcium and phosphate levels
Mechanotransduction detects mechanical forces and translate them into myologic activity
Osteocytes
Specialized multinucleated macrophages derived
from circulated monocytes
Responsible for bone resorption
Osteoclast
Attaches to the bone matrix which creates sealed extracellular trench (resorption pit)
Secretion of acid and neutral proteases, (MMPs), into the pit results in dissolution of inorganic and organic
bone components
Osteoclast
Most bones that form during embryogenesis develop from a
cartilage mold via
endochondral ossification
Central medullary canal within the anlagen is created by
chondroblasts at approximately
8 week of gestation
earliest bone trabeculae
Primary Spongiosa
Dense layer of mesenchyme is directly ossified by
osteoblasts without a cartilage anlagen
Intramembranous Ossification
Maintains chondrocyte proliferation
Growth hormone
Acts on proliferating chondrocytes to induce
hypertrophy
Thyroid Hormone
Coordinates chondrocyte proliferation and
differentiation with osteoblast proliferation
Indian Hedgehog
Activates the PTH receptor to maintain
chondrocyte proliferation
PTHrP
Activate β-catenin to promote chondrocyte
proliferation and maturation
WTN Growth Factors
Expressed by proliferating, but not
hypertrophic, chondrocytes that is essential for
differentiation of chondrocyte precursors
SOX9
Expressed in early hypertrophic chondrocytes
which controls terminal chondrocyte and
osteoblast differentiation
RUNX2
Act on hypertrophic chondrocytes to inhibit
proliferation and promote differentiation
Fibroblast Growth Factor
Chondrocyte proliferation and hypertrophy at
the growth plate
Bone Morphogenic Proteins
Remodeling takes place at
Bone Multicellular Unit (BMU)
Balance between bone formation and resorption is modulated by
RANK & WNT
expressed on osteoclast
precursor
Transmembrane receptor RANK
expressed on osteoblasts and marrow stromal cells
RANK ligand
“decoy” receptor made by osteoblasts;
prevents interaction with RANK
Osteoprotegerin
hormones, vitamin D, inflammatory
cytokines and growth factors
Systemic factors
Systemic Factors:
osteoclast differentiation -
increased bone turnover
PTH, IL-1 and glucocorticoids-
Systemic Factors:
favor OPG
expression or block osteoclast activity
Bone morphogenic proteins and sex hormones
Peak bone mass is achieved in ____ after cessation of _______
Early adulthood; skeletal growth
resorption = formation —–> decline in skeletal mass happens when
4th decade
localized disruption of the migration and
condensation of the mesenchyme
Dysostoses
May occur in isolation or as part of more complex syndromes
Caused by defects in mesenchymal condensation and
differentiation into cartilage anlage
Dysostoses
Complete absence of a bone or entire digit
aplasia
extra bones or digits
supernumerary digit
abnormal fusion of bones
syndactyly, carniosynostosis
Complete absence of a bone or entire digit
Dysplasia
Arise from mutations in genes that control development
or remodeling of the entire skeleton
Implies abnormal growth, bbut it is not a precursor of
neoplasia, as is the case with dysplasias of epithelial cells
Dysplasia
caused by mutations in the homeobox HOXD13 gene and are characterized by shortening of the terminal phalanges of the thumb and big toe
Brachydactyl types D & E
global disorganization of bone and/or cartilage
Dysplasia
loss of function mutation in RUNX2
Cleidocranial dysplasia
Characterized by:
Patent fontanelles
Delayed closure of cranial sutures
Wormian bones (extra bones that occur within a cranial suture)
Delayed eruption of secondary teeth
Primitive clavicles
Short stature
Cleidocranial Dysplasia
most common skeletal dysplasia and a major
cause of dwarfism
Achondroplasia
Autosomal dominant disorder caused by gain-of-function
mutations in the FGF receptor 3 (FGFR3) gene
Achondroplasia
Retarded cartilage growth results in:
Shortened proximal extremities
Enlarged head with bulging forehead
Depression of the root of the nose despite a trunk of relatively normal length
Achondroplasia
most common lethal form of dwarfism
Thanatophoric dysplasia
Micromelic limbs, frontal bossing, relative macrocephaly,
small chest cavity, and bell-shaped abdomen
Thanatophoric Dysplasia
HOXD13
Transcription
factor
Short, broad terminal
phalanges of first digits
Brachydactyly
types D and E
SOX9
Transcription
factor
Sex reversal, abnormal
skeletal development
Camptomelic
dysplasia
RUNX2
Transcription
factor
Abnormal clavicles,
Wormian bones,
supernumerary teeth
Cleidocranial
dysplasia
TBX5
Transcription
factor
Congenital abnormalities,
forelimb anomalies
Holt-Oram
syndrome
LMXIB
Transcription
factor
Hypoplastic nails,
hypoplastic or aplastic
patellas, dislocated radialhead, progressive
nephropathy
Nail-patella
syndrome
PAX3
Transcription
factor
Hearing loss, abnormal
pigmentation, craniofacial
abnormalities
Waardenburg
syndrome types 1
and 3
FGFR3
Receptor
Short stature, rhizomelic
shortening of limbs,
frontal bossing, midface
deficiency
Achondroplasia
FGFR3
Receptor
Disproportionately short stature, micromelia,
relative macrocephaly
Hypochondroplasia
LRP5
Receptor
Increased bone density,
hearing loss, skeletal
fragility
Osteopetrosis,
autosomal dominant
RANKL
Receptor - ligand
Increased bone density
Osteopetrosis,
infantile form
LRP5
Receptor
Congenital or infantonset loss of vision, skeletal fragility
Osteoporosispseudoglioma syndrome
FGFR3
Receptor
Severe limb shortening
and bowing, frontal
bossing, depressed nasal bridge
Thanatophoric
dysplasia
COL2A1
Type II
collagen
Short trunk
Achondrogenesis
type 2
COL10A1
Type X
collagen
Mildly short stature
Metaphyseal dysplasia,
Schmid type
COL1A1,
COL1A2
Type 1
collagen
Bone fragility
Osteogenesis
imperfecta types 1-4
CA2
Carbonic
anhydrase
Increased bone density,
fragility, renal tubular
acidosis
Osteopetrosis
with renal tubular acidosis
CLCN7
Chloride
channel
Increased bone density,
fragility
Osteopetrosis,
late onset type 2
