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Anatomy and Histology by Luis Filgueira

What is bone?

Connective Tissue

Cells <>

Bone forming cells <> Bone resorbing cells Organic matrix <> Inorganic matrix <>Calcium apatite

Bone Tissue <>

Function(s)?

What is ?

Connective Tissue

Cells <> Extracellular Matrix Cells =

Bone <> Cartilage

YES Calcified Matrix NO YES Blood vessels/nerves NO YES Repair/Remodelling NO

1 Bone = live tissue with high turnover = specialised connective tissue

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. Connective tissue proper <> /fibrocytes 2. Fat tissue <> Adipocytes 3. Cartilage <> Chondrocytes 4. Bone <> /

Extracellular matrix produced and secreted by the cells 1. 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

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 = 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

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

Osteoblast Muscle Cell

Fat Cell/Lipocyte

Osteocyte

3 principles of formation

Direct formation of bone tissue Embryonic bone formation = Bone remodelling intramembranous Bone repair Formation of cartilage tissue = Only during embryology cartilage skeleton

First formation of cartilage model and secondary replacement of Embryonic bone formation cartilage by bone tissue = Bone growth enchondral ossification

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 of the skull Bone repair

Differentiation of stem cells to osteoblasts

Production of Cells enclose extracellullar themselves into matrix 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 Stromal Stem Cell

RUNX2

Osteoprogenitor Cell Fibroblast

Osteoblast Muscle Cell

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

Osteoprogenitor Cell Fibroblast PPAR

Osteoblast Muscle Cell

Fat Cell/Lipocyte

Osteocyte

8 Osteoblasts/osteocytes

SOX9 Chondrocyte Stromal Stem Cell

RUNX2

Osteoprogenitor Cell Fibroblast PPAR

Wnt Osteoblast Muscle Cell

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