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Bone

Anatomy and Histologyby

Luis Filgueira

What is bone?

Connective Tissue

Cells <> Extracellular Matrix

Bone forming cells <> Bone resorbing cells

Bone Tissue <> Bone Marrow

Organic matrix <> Inorganic matrix

Collagen <>Calcium apatite

Function(s)?

What is cartilage?

Connective Tissue

Cells <> Extracellular Matrix

Bone <> Cartilage

Calcified Matrix

Blood vessels/nerves

Repair/Remodelling

YES

YES

YES

NO

NO

NO

Cells = Chondrocytes

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= live tissue with high turnover

= specialised connective tissue

Principles of connective tissue

Cells <> Extracellular matrix

Types of connective tissue

1. Embryonic connective tissue

2. Connective tissue proper

3. Fat tissue

4. Cartilage

5. Bone

Bone

Cells <> Extracellular matrix

Principles of connective tissue

Cells1. Connective tissue proper <> Fibroblasts/fibrocytes

2. Fat tissue <> Adipocytes

3. Cartilage <> Chondrocytes

4. Bone <> Osteoblasts/osteocytes

Extracellular matrix

produced and secreted by the cells1. Ground substance

2. Fibres

3. Minerals

4. 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

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Addition/growth of bone = appositional growth

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

Osteoprogenitor cells are recruited onto the bone surface

Teitelbaum and Ross, Nature Reviews Genetics 2003, 4, 638

Differentiation and function of osteoclasts

is under tight control of osteoblasts

Osteoclasts

Haematopoietic Stem Cell

Blood Monocyte

MacrophageOsteoclast Dendritic cell

Erythrocyte

Lymphocyte

Granulocyte

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What happens if there is no RANK?

Osteoblasts/osteocytes

Stromal Stem Cell

Osteoprogenitor Cell

Osteoblast

Osteocyte

Fat Cell/Lipocyte

Muscle Cell

Fibroblast

Chondrocyte

3 principles of skeleton formation

Direct formation of bone tissue

=

intramembranous ossification

Formation of cartilage tissue

=

cartilage skeleton

First formation of cartilage model

and secondary replacement of

cartilage by bone tissue

=

enchondral ossification

Embryonic bone formation

Bone remodelling

Bone repair

Only during embryology

Embryonic bone formation

Bone growth

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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

Matrix is calcified

Osteocytes = functional syncytium

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First formation of cartilage model

and secondary replacement of

cartilage by bone tissue

=

enchondral ossification

Alcian blue / Alazarin red

Enchondral ossification

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Osteoblasts/osteocytes

Stromal Stem Cell

Osteoprogenitor Cell

Osteoblast

Osteocyte

Fat Cell/Lipocyte

Muscle Cell

Fibroblast

ChondrocyteSOX9

RUNX2

Cbfa1/Runx2

Deficiency

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Cbfa1/Runx2

RUNX2 mutation

Holoprosencephaly and cleidocranial

dysplasia in a patient due to two positioneffect

mutations

Osteoblasts/osteocytes

Stromal Stem Cell

Osteoprogenitor Cell

Osteoblast

Osteocyte

Fat Cell/Lipocyte

Muscle Cell

Fibroblast

ChondrocyteSOX9

RUNX2

PPAR

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Osteoblasts/osteocytes

Stromal Stem Cell

Osteoprogenitor Cell

Osteoblast

Osteocyte

Fat Cell/Lipocyte

Muscle Cell

Fibroblast

ChondrocyteSOX9

RUNX2

PPAR

Wnt

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Oropharyngeal Skeletal Disease

Accompanying High Bone Mass and Novel LRP5 Mutation

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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

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Bone Morphogenetic Protein

BMP

Joints

Nuclear Transcription Factors

Soluble Extracellular Factors

Summary of cells and factors