B6.068 Prework 1: Bone Development Overview / Appendicular Skeleton Flashcards
why is bone a tissue?
mineralized connective tissue
comprised of different cell types that communicate with one another
continuously remodeled
processes under local and systemic hormonal control
how is bone modeling orchestrated
by osteocytes in response to mechanosensors
local control of bone modeling
growth factors
cytokines
systemic hormonal control of bone modeling
calcitonin
estrogen
why is bone an organ
collectively comprises the skeletal system
functions of the skeletal system
locomotion
structural support
protection for internal organs
mineral reservoir for calcium and phosphate (Ca homeostasis)
contains bone marrow which produces red and white blood cells
endocrine regulation
endocrine function of bone
produces osteocalcin
hormone that has a role in bone mineralization, calcium ion homeostasis, and insulin metabolism
embryologic components of the skeletal system
a) paraxial mesoderm
b) lateral plate mesoderm (parietal)
c) cranial neural crest cells
d) mesenchyme of dermis
how does the paraxial mesoderm contribute to the skeletal system
forms somitomeres cranially and somites from the occipital to sacral region
ventral portion of the somite
sclerotome
sclerotome contribution to skeleton
becomes mesenchymal at the end of the 4th week
comprised of loosely organized connective tissues
mesenchymal cells can migrate and differentiate to form multiple cell types (fibroblasts, chondroblasts, osteoblasts)
caudal portion gives rise to vertebral column and ribs
cranial vault and base of skull origin
paraxial mesoderm:
somitomeres
occipital somites
parietal lateral plate mesoderm contribution to skeletal system
bones of pelvic and shoulder girdles
long bones of limbs
sternum
neural crest cell contribution to skeletal system
bones of face and skull
mesenchyme of dermis contribution to skeletal system
flat bones of the skull
osteoblast origin
mesenchymal stem cells in periosteum
osteoblast function
secrete the matrix (collagen 1 rich osteoid)
catalyze mineralization (calcification) of osteoid via secretion of alk phos to make bone
become trapped in the matrix they secrete
osteocytes
mature bone cells w dendritic processes formed when osteoblasts become trapped maintain bone role in mineral homeostasis via FGF23 sense mechanical load viable for decades
osteoclasts
dissolve/absorb bone during growth by secreting H+ and collagenases
osteoclast origin
differentiate from a fusion of monocyte/ macrophage lineage precursors to form large multinucleate bone cells
RANK signaling pathway
regulates osteoclast differentiation and activation, and bone remodeling/repair
RANK
receptor activator for NFKB
- TNF receptor family
- present on pre-osteoclasts and osteoclasts
RANK-L
expressed by osteoblasts
activates RANK & transcription factor NFKB
role in osteoclast formation, differentiation and survival
chondroblasts
mesenchymal progenitor cells which will form chondrocytes in the growing cartilage matrix
chondrocytes
produce and maintain the cartilaginous matrix
articular + hyaline model for bone formation
chondroclasts
involved in resorption of calcified cartilage
multinucleated (giant) cells
discuss the steps of neural crest cells forming craniofacial cartilage and bone
- arise from border of non neural and neural ectoderm
- neural ectoderm rolls up to form neural tube
- epithelial cells in dorsal portion of the neural tube undergo epithelial to mesenchymal transformation
- neural crest migrate out and away from neural tube
- forms head and neck
compact bone
cortical
hard, dense, found near surface where strength is required
spongy bone
cancellous, trabecular
mesh like, found in ends of long bones and center of flat bones
bone marrow
loose CT that fills cavities of bone
produces red and white blood cells
periosteum
CT on the surface of bone
outer fibrous layer = nerves and BVs
inner layer = osteogenic cells
endosteum
inner lining of bones
lines bone marrow cavity
Haversian canal
duct in bone w blood vessels
Osteon / Haversian system
functional unit of compact bone
canalicular system of bones
tiny canals extending from one lacuna to another
connect osteocytes
vascularity of bones
bone cells must be in close proximity to capillaries
vessels present in bone marrow, Haversian canals, and periosteum
elongation of bones
involves epiphysial cartilages at the ends of the long bone, but it is the diaphysis that increases in length
newly formed bone vs matured bone
new: appears woven w haphazard strands of collagen
eventually transforms to be lamellar (parallel arrays of mineralized osteoid)
4 phases of skeletal development
- migration of pre-skeletal mesenchymal cells to sites of future skeletogenesis
- interaction of mesenchymal cells with epithelial cells
- interaction leads to mesenchymal condensation
- followed by differentiation to chondroblasts or osteoblasts
2 types of bone formation
intramembranous ossification
endochondral ossification
intramembranous ossification
mesenchyme differentiated directly into osteoblasts, which form bone
e.g. flat bones of skull
endochondral ossification
mesenchymal cells give rise to chondroblasts, which differentiate to chondrocytes which make mineralized cartilage models
cartilage models replaced by bone
e.g. base of skull, limb long bones, end of irregular bones (ribs and vertebrae)
steps of intramembranous ossification
- mesenchymal cells group into clusters and form multiple cell types; osteoblasts form ossification centers
- secreted osteoid becomes calcified and traps osteoblasts which become osteocytes
- trabecular matrix forms from osteoid and periosteum forms from surface osteoblasts
- compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red marrow
time line of intramembranous ossification
begins in utero
continues into adolescence
last bones to ossify
flat bones of face (at end of adolescence)
benefits of later intramembranous ossification
skull sutures and clavicles are not fully ossified at birth, skull and shoulders deform during passage through the birth canal
skull can increase in size to allow for postnatal bone growth
primary ossification centers
part of endochondral ossification
present in long bones by week 12 of development
responsible for prenatal bone growth
secondary ossification centers
ends of bone
where growth progresses after birth
epiphysis
articular portion of long bones
metaphysis
site of secondary ossification 3 subportions: -epiphysial plate (cartilaginous) -bony portion -fibrous component (periphery of growth plate)
diaphysis
midportion (shaft)
portion of bone that contains the medullary cavity
lengthens due to action of growth plates in metaphyses
contains primary ossification center
how does the primary ossification center form
- mesenchymal cells differentiate into chondroblasts, then chondrocytes
- cartilage model of the future bony skeleton and perichondrium form
- capillaries penetrate cartilage, bringing osteoblasts / perichondrium transforms to periosteum / periosteal collar develops around mineralized cartilage / primary ossification center develops (in diaphysis)
- cartilage and chondrocytes continue to grow at ends of the bone
development of secondary ossification centers
at birth: the diaphysis is ossified and 2 ends of bone are still cartilaginous
vessels invade epiphyses
secondary ossification continues in epiphyses
when do epiphysial plates disappear
approx. age 13-15 in females, 15-17 in males
bone age information
derived from ossification centers in hands and wrists
how is a cartilage model formed
chondrocytes secrete collagen type 2 and sulfated proteoglycans
what happens after a cartilage model is formed
chondrocytes move away from ends of bone, begin to hypertrophy & secrete alk phos
collagen is reorganized into hexagonal lattices due to production of collagen type X
ECM becomes calcified by calcium phosphate
chondrocytes eventually undergo apoptosis
why do chondrocytes undergo apoptosis?
matrix mineralizes and nutrients can no longer reach them because cartilage is avascular
what happens when chondrocytes die?
secrete matrix metalloproteinases to degrade ECM
blood vessels invade resulting spaces, enlarging the cavities and bringing osteoblasts and chondroblasts
what are the 5 zones of the epiphyseal plate
EPIPHYSIS reserve/ resting zones proliferation zone hypertrophic cartilage zone zone of calcification of cartilage zone of ossification
reserve/resting zone
chondrocytes anchor plate to osseous tissue of epiphysis
proliferation zone
chondrocytes proliferation
hypertrophic cartilage zone
chondrocytes increase in size, accumulate alk phos
zone of calcification of cartilage
chondrocytes apoptose; cartilaginous matrix begins to calcify
zone of ossification
osteoclasts and osteoblasts from the diaphyseal side break down the calcified cartilage and replace with mineralized bone (type 1 collagen)
what types of bones undergo appositional growth
occurs in all bones!
when bones increase in length, they also increase in diameter
diameter growth continues after longitudinal growth ceases
cells involved in appositional growth
osteoclasts resorb old bone that lines the medullary cavity
osteoblasts produce new bone tissue beneath periosteum
subperiosteal cortical bone forms and an increase in bone diameter results
how many bones in the shoulder girdle
4
clavicle and scapula each side
how many bones in the arm and forearm
6
humerus, ulna, radius
how many bones in the hand
58 16 carpals 10 metacarpals 28 phalanges 4 sesamoid
how many leg bones
8
femur, tibia, patella, fibula
epidemiology of achondroplasia
most common form of skeletal dysplasia
1/20,000 live births
genetics of achondroplasia
autosomal dominant
related to FGF Receptor 3 mutations
systems impacted by achondroplasia
endochondral ossification in long bones and formation of base of skull
effects of achondroplasia
short limbs and fingers
large skull
small midface
prominent forehead
effects of Marfan Syndrome
long limbs long face sternal defects dilation and dissection of ascending aorta lens dislocation
genetics of Marfan
fibrillin 1 gene mutations
when do symptoms of Marfan appear?
symptoms may not appear / be diagnosed until late in childhood / early adulthood
what is congenital hyperpituitarism
production of excess growth hormone
acromegaly
growth of soft tissues (enlargement of face), ad bones of hands and feet
gigantism
excessive growth (height and body proportions)
what is hypopituitarism
growth hormone is affected
effects of hypopituitarism
short stature
fat around waist and face
delayed teeth development
sluggish hair growth
congenital rickets
caused by severe maternal def in vit D
rare
results in defective mineralization of cartilaginous plates
what is osteogenesis imperfecta
reduced type 1 collagen production and altered bone matrix
hypomineralization of the long bones of limbs
improper bones form
bone effects of osteogenesis imperfecta
shortened, bowed, easily fractured bones
frequent and multiple fractures
bowing of bones and curvature of spine can result in short stature
genetics of osteogenesis imperfecta
90% linked to defects in COL1A1 or COL1A2
non-bone effects of osteogenesis imperfecta
skin, muscles, joints, teeth, hearing, blue sclera
