Bone development Flashcards
Where does bone tissue originate from?
Mesodermal (mesenchymal) germ layer
What two types of mesodermal germ layers exist?
Lateral plate mesoderm
Paraxial mesoderm
What bones does the lateral plate mesoderm give rise to?
Limb and long bones
What skeleton does the lateral plate mesoderm give rise to?
Appendicular skeleton
What skeleton does the paraxial mesoderm give rise to?
Axial skeleton
What are the three distinct lineages that generate the skeleton?
Somites - axial skeleton
Lateral plate mesoderm - limb skeleton
Cranial neural crest - branchial arch and craniofacial bones and cartialge
What skeleton do the somites form?
Axial skeleton
What skeleton does the lateral plate mesoderm form?
Limb skeleton
What skeleton does the cranial neural crest form?
Branchial arch and craniofacial bones
What are the two major modes of bone formation?
Intramembranous ossification
Endochondral ossification - long bones
What do endochondral ossification and intramembranous ossification have in common?
They both involve the transformation of a preexisting mesenchymal tissue into bone tissue
What does intramembranous ossification entail?
Direct conversion of mesenchymal tissue into bone
Characteristic way in which flat bones of the skull are formed
Steps of intramembranous ossification
Neural crest-derived mesenchymal cells proliferate and condense into compact nodules
Some of these cells develop into capillaries and some become osteoblasts
Osteoblasts secrete osteoid matrix
The osteoid matrix becomes calcified
Osteoblasts are separated from the region of calcification by the matrix they secrete
Ocassionally they become trapped in the calcified matrix and become osteocytes
Calcification proceeds and bony spicules radiate out from the region where ossification began
The entire region of calcified spicules becomes surrounded by mesenchymal cells that form the periosteum
What is the osteoid matrix composed of?
Collagen-proteoglycan matrix
Can bind calcium salts
What cells compose the periosteum that surround the bone?
Cells on the inner surface of the periosteum become osteobladts and deposit osteoid matrix
Many layers of bone are formed
What are important factors in intreamembranous ossification?
BMPs
CBFA1 transcription factors
What are BMPs?
Bone morphogenetic proteins
Released by head epidermis
Instruct the neural crest-derived mesenchymal cells to become osteoblasts
By activating CBFA1 gene in mesenchymal cells
Also activate genes for osteocalcin, osteopontin and other bone-specific ECM proteins
What happened to mice lacking the CBFA1 gene?
Died shortly after birth
Showed skeletal defects
Skeletons lacked bone
What happened to mice with heterozygous CBFA1?
Stunted growth
Clavicle - absent or deformed
Skull sutures fail to close
What does endochondral ossification entail?
Formation of cartilage tissue from aggregated mesenchymal cells
Subsequent replacement of the HYALINE cartilage by bone
What are the 5 processes of Endochondral ossification?
Bone collar formation
Cavitation
Periosteal bud invasion
Diaphysis elongation
Epiphiseal ossification
Boys cant pee during erections
Describe the process of bone collar formation
Primary ossification center develops in the center of the hyaline cartilage
This is the source of bone formation
Mesenchymal cells in the perichondrium differentiate int osteoblasts
Start to secrete osteoid against the diaphysis
The hyaline cartilage diaphysis is now encased in compact bone
This bone collar gives developing bone structural support to begin hardening
Describe the process of cavitation
Chondrocytes stop dividing and instead increase in size dramatically - hypertrophy
Hypertrophic condrocytes secrete membrane-bound vesicles into the ECM containing enzymes active in the generation of calcium and phosphate ions
This hardening is called calcification - happens from the center
Calcified hyaline cartilage is now impermeable to diffusion of nutrients
Since the chondrocytes can’t receive any nutrients -> begin to die
When they die they leave small cavities -> allow for blood vessels to travel through
Describe the process of periosteal bud invasion
The dying chondrocytes signal to the body about their anaerobic environment
Previously nutrients were deliveres through cartilage through simple diffusion
The periosteal region is invaded by a bud containing blood vessels and nerves
Allows nutrients and oxygen to enter the cavities previously inhabited by chondrocytes
Osteoblasts and osteoclasts take advantage of this highway into the bone and enter the bone along with nutrients
The osteoblasts secrete osteoid into the remaining hyaline cartilage -> gives rise to early spongy bone
Describe the process of diaphysis elongation
After the nutrient source is delivered to the center of the bone, the diaphysis region has the resources to elongate
Elongated region is powered by cells dividing in the primary center of ossification
Elongated region = medullary cavity - where bone marrow is contained
Descrive the process of epiphyseal ossification
Just before birth - epiphysis will develop own centers of ossification
As they can’t remain made of cartilage -> structurally weak
These are secondary centers of ossification
What are secondary centers of ossification?
Centers of ossification that develop in the epiphysis just before birth to allow the hyaline cartilage to develop into bone
Why do we need secondary centers of ossification? Why can’t bones grow completely from the center?
Region between the primary and secondary centers of ossification = epiphyseal plate
AKA growth plate
Remaining cartilage from hyaline model
How bones grow as we age
As long as the epiphyseal growth plates are able to produce chondrocytes, the bone continues to grow
What acts as a model for the bone that is formed?
Hyaline cartilage
Describe the process by which hyaline cartilage is formed
Mesenchymal stem cells comit to become chondrocytes
The commited mesenchyme cells condense into compact nodules and differentiate into chondrocytes
What causes the mesenchymal cells to become chondrocytes?
Paracrine factors
Causes the mesenchymal cells to express Pax1 and Scleraxis
Transcription factors
Activate cartilage-specific genes
What initiates the condensation of chondrocytes to form nodules?
N-cadherins
N-CAM
SOX9 gene - expressed in pre-cartilagenous condensations
