Skeletal Morphogenesis and Bone Composition

components of the human skeleton

bones and cartilage connected by a network of tendons and ligaments

three groups of the skeleton

1. craniofacial bones (skull, associated bones)
2. axial skeleton (spine, rib cage)
3. appendicular skeleton (upper and lower extremities)

functions of bone

1. structural: supports and insertions, strength and shape for body, movement/motion
2. protective: protection of organs, nerves, and blood vessels
3. metabolic: mineral homeostasis, endocrine regulation, hemopoiesis

extracellular matrix of bone

98% of bone
responsible for structure and strength
organic and inorganic components

organic component of bone ECM

1. fibers (collagen)
2. ground-substance

inorganic component of bone ECM

hydroxyapatite and minerals

cells of bone CT

2% of bone
responsible for bone function
includes: bone cells, macrophages, mast cells, MSCs, osteoprogenitor cells, WBCs, etc

Where do the craniofacial bones develop from?

1. anterior skull: intramembranous ossification
2. base of skull and sides: endochondral ossification

What are the two ossification patterns

1. intramembranous
2. endochondral

endochondral ossification

cartilage forms before the bone forms

intramembranous ossification

bone forms at the matrix

Where does each part of the skeleton develop from?

1. Craniofacial bones: neural crest
2. Axial Skeleton: paraxial mesoderm
3. Appendicular Skeleton: lateral plate mesoderm

Bone modeling

shaping of bone; completed by early adulthood (1 & 2 decades of life)

bone remodeling

ongoing replacement of old bone tissue by new bone tissue, continuous throughout life and essential for growth

two types of bone

1. compact/dense (outer sides of bones, protective)
2. spongy/cancellous/trabecular (inner side of bones)

Woven vs Lamellar

woven: immature bone, irregular fiber arrangement
lamellar: mature and regularly arranged collagen

structure of flat bone

external/internal surfaces are compact bone
middle layer (diploe) is spongy bone
the spongy middle layer absorbs shock to protect inner components

osteon

basic unit structure of mature (lamellar) bone

Three components of mature bone

1. compact lamellar bone (outer)
2. spongy/trabecular bone (inner)
3. blood supply from marrow

Haversian Canals

passageways running parallel to the surface of a bone that contain capillaries and nerve fibers, lined with osteoprogenitor cells and osteoblasts

Volkmann's Canals

channels through which blood vessels and nerves travel from the bone's surface to interior (perpendicular to Harversian canal)

periosteum

outer dense CT layer of osteoblastic cells and vessels

endosteum

inner CT layer of osteoblastic cells and vessels

Canaliculi

spaces surrounded by mineralized bone, used for passive diffusion and transport

lacunae

spaces where osteocytes are trapped within the mineralized bone of the osteon

trabeculae (cancellous bone)

spongelike rods and plates of bone, in between which are spaces filled with marrow, lightweight but strong

osteoclasts

Bone-destroying cells (bone resorption)
responsible for bone remodeling and for transforming non-lamellar bone to lamellar
reside in Howship's lacuna

two components of the bone matrix (osteoid)

organic component (35%)
inorganic component (65%)

organic component of osteoid

35%
made of Type I collagen fibers and non-collagenous proteins
enzymes
the ground substance

inorganic component of osteoid

65%
calcium phosphate deposits, minerals
provides structural resilience

osteoblasts

bone forming cells ("b" is for build)
flattened squamous cells that form osteocytes (mature bone cells0
derived from osteoprogenitor stem cells/multipotent mesenchymal stem cells

osteocytes

bone maintain cells trapped in the bone matrix (lacuna), transmit mechanical signals through gap junctions in canaliculi, maintain ECM

Lining cells

protect and cover the bone's surface, including periosteal and endosteal cells, cover bone that is not remodeling to maintain and nutritionally support osteocytes

mesenchymal cells (marrow stromal/MSCs)

the source of the osteoblast cell lineage

monocyte

macrophage lineage cells, osteoclast precursors

osteogenesis

induced by members of bone morphogenetic protein (BMP)

mesenchymal stems cells (postnatal stem cells)

give rise to osteoprogenitor cells and differentiate to form many other cells, such as osteoblasts and fibroblasts

four steps of bone formation

1. collagen deposition (Type I)
2. secretion of ground substance
3. crystal seeding (osteoblasts secrete calcium phosphate)
4. mineralization & maturation (hydroxyapatite formation, bone matrix forms)

two layers of the periosteum

1. outer layer (fibrogenic)
2. inner layer (osteogenic)

Osteoclastogenesis

a signaling process that activates osteoclasts
trigged by M-CSF and RANKL

Macrophage colony-stimulating factor (M-CSF)

stimulates conversion of monocyte to macrophage when it binds, macrophage then expresses RANK

Receptor Activator of Nuclear Factor Kappa B RANK)

expressed by macrophage, binds to RANKL (RANK + ligand) on osteoblast or stromal cell

role of macrophages in osteoclastogenesis

express RANK, bind RANKL, commit to osteoclastogenesis

osteoclastic bone resorption

the removal of dead bone during bone modeling and bone remodeling, included dissolved components of the bone matrix