Bone
Anatomy and Histology
by
Luis Filgueira
What is bone?
Connective Tissue
Cells <> Extracellular Matrix
Bone forming cells <> Bone resorbing cells
Organic matrix <> Inorganic matrix
Collagen <>Calcium apatite
Bone Tissue <> Bone Marrow
Function(s)?
What is cartilage?
Connective Tissue
Cells <> Extracellular Matrix
Cells = Chondrocytes
Bone <> Cartilage
YES
YES
YES
Calcified Matrix
Blood vessels/nerves
Repair/Remodelling
NO
NO
NO
1
= live tissue with high turnover
= specialised connective tissue
Bone
Principles of connective tissue
Types of connective tissue
1. Embryonic connective tissue
2. Connective tissue proper
3. Fat tissue
4. Cartilage
5. Bone
Cells <> Extracellular matrix
Principles of connective tissue
Cells <> Extracellular matrix
Cells
1.
2.
3.
4.
Connective tissue proper
Fat tissue
Cartilage
Bone
<> Fibroblasts/fibrocytes
<> Adipocytes
<> Chondrocytes
<> Osteoblasts/osteocytes
Extracellular matrix
produced and secreted by the cells
1.
2.
3.
4.
Ground substance
Fibres
Minerals
Water
Bone remodelling
Continuous adaptation of bone depending on
Age
Mechanics
Hormones
Nutrition
Formation of new bone tissue
Resorption of old bone tissue
Osteoblasts
Osteoclasts
2
Addition/growth of bone = appositional growth
Osteoprogenitor cells are recruited onto the bone surface
Osteoblasts
Arrange in a row on the surface of bone
Produce new matrix = osteoid
Enclose themselves inside the matrix
Osteoblasts become osteocytes
New matrix is calcified
Differentiation and function of osteoclasts
is under tight control of osteoblasts
Teitelbaum and Ross, Nature Reviews Genetics 2003, 4, 638
Osteoclasts
Haematopoietic Stem Cell
Erythrocyte
Granulocyte
Blood Monocyte
Lymphocyte
Osteoclast
Macrophage
Dendritic cell
3
What happens if there is no RANK?
Osteoblasts/osteocytes
Chondrocyte
Stromal Stem Cell
Osteoprogenitor Cell
Fibroblast
Muscle Cell
Osteoblast
Fat Cell/Lipocyte
Osteocyte
3 principles of skeleton formation
Direct formation of bone tissue
=
intramembranous ossification
Embryonic bone formation
Bone remodelling
Bone repair
Formation of cartilage tissue
=
cartilage skeleton
First formation of cartilage model
and secondary replacement of
cartilage by bone tissue
=
enchondral ossification
Only during embryology
Embryonic bone formation
Bone growth
4
Mesenchymal cells
of head and
neural crest
3 principles of skeleton formation
intramembranous ossification
most of skull
cartilage skeleton
Nose
Ears
Larynx
Articular cartilage
enchondral ossification
Axial skeleton
Skeleton of limbs
Primary bone tissue <> Intramembraneous ossification
Embryonic formation of most bones of the skull
Bone repair
Differentiation of stem cells to
osteoblasts
Production of
extracellullar
matrix
Cells enclose
themselves into
the matrix
Osteoblasts become osteocytes
Osteocytes = functional syncytium
Matrix is calcified
5
First formation of cartilage model
and secondary replacement of
cartilage by bone tissue
=
enchondral ossification
Alcian blue / Alazarin red
Enchondral ossification
6
Osteoblasts/osteocytes
SOX9
Chondrocyte
Stromal Stem Cell
RUNX2
Osteoprogenitor Cell
Fibroblast
Muscle Cell
Osteoblast
Fat Cell/Lipocyte
Osteocyte
Cbfa1/Runx2
Deficiency
7
Cbfa1/Runx2
Holoprosencephaly and cleidocranial
dysplasia in a patient due to two positioneffect
mutations
RUNX2 mutation
Osteoblasts/osteocytes
SOX9
Chondrocyte
Stromal Stem Cell
RUNX2
Fibroblast
Osteoprogenitor Cell
PPAR
Muscle Cell
Osteoblast
Fat Cell/Lipocyte
Osteocyte
8
Osteoblasts/osteocytes
SOX9
Chondrocyte
Stromal Stem Cell
RUNX2
Fibroblast
Osteoprogenitor Cell
PPAR
Wnt
Muscle Cell
Osteoblast
Fat Cell/Lipocyte
Osteocyte
9
Oropharyngeal Skeletal Disease
Accompanying High Bone Mass and Novel LRP5 Mutation
10
Why enchondral ossification?
1. Bone template of cartilage
2. Longitudinal growth
3. Articular cartilage
Most bones undergo
enchondral ossification
Enchondral ossification
Epiphyseal growth plate
<>
Longitudinal bone growth
11
Bone Morphogenetic Protein
BMP
Joints
Summary of cells and factors
Soluble Extracellular Factors
Nuclear Transcription Factors
12