Bone tissue : . remodeling . . - ECM .calcification : 1. skeleton . . 2. : . 3. hematopoietic bone marrow , . Adult stem cells , . 4. calcium phosphate, .calcium homeostasis ' , . , . . brittle . . remodeling : 1. . 2. ) , , (. 3. . 4. .

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2 : 1. : ( trabecular bone, cancellous bone) Spongy bone " " ) spicules or trabeculae (. . . 2. : (cortical bone) Compact cone . .

** 2 " compact bone .spongy bone

: The Skeletal System

Bone

Compact bone

Spongy bone

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: 1. long bones . 2. flat bones . 3. irregular bones . ** " .

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: : 1. - : Decalcification o .wax embedding o formic acid nitric acid . o - . o / EDTA , - ) (. - EDTA . 2. : Ground section o . o - canaliculi ) cell lacunae (. 3. : o resin ) ( ).(tungsten-carbide o " .

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: : long bones ) (shaft ,diaphysis ) epiphyses (. elongation .metaphysis ) (shaft ) .(cortical or diaphyseal bone )( ,spongy )( - .articular cartilage ) periosteum (. endosteum . - Periosreum- Endosteum )(bone-forming cells osteoprogenitor cells .osteogenic potential . .

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: flat bones membrane bones . ) '( : 1. .outer table 2. .diploe 3. .inner table periosteum ) ( - periosteum ) duramater (.

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: : Bone matrix " )( ) (. - .intercellular calcified bone matrix 2 : 1. : organic matrix 1 )-%59( .amorphous ground substance

:. ): sulfated GAG's (glycosaminoglycans 3 : .Chondroitin-4-sulfate o .Chondroitin-6-sulfate o .Keratin sulfate o . bone proteins : .osteocalcin ,bone sialoprotein " . - osteocalcin remodeling . ** - sulfated GAG's acidophilic ).(H&E 2. : Inorganic salts .hydroxyapatite ) ( . hydroxypatite ) , ( . )%03( Organic matrix )%2( Cells )%89( Matrix )%07( Inorganic matrix )%59( Hydroxyapatite

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: Bone cells 1. : Osteoprogenitor cells o, .mesenchyme o , mesenchyme-like - periosteum- ) endosteum (. )( ) - .(osteogenic .Osteoprogenitor cells

o .RER 2. : Osteoblasts o -.osteoprogenitors o . o . o - bone matrix ,RER ' . o ) (. o- Osteoblasts alkaline phosphatase . , . o - osteoblasts osteoid .prebone . o matrix vesicles - Osteoblast , - osteoblast , .

Osteoblasts

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3. : Osteocytes o - osteoblasts lacunae - .bone matrix o canaliculi . - GAP junction 2 . o , . o - .canaliculi

4. : Osteoclasts o ) 001-02 (. o ) -05 (. o bone resorption .Howship's lacunae o " - osteoclasts ,"ruffled "border

.Howship's lacunae o- Osteoclasts ) ( , ' . o acid phosphatase - .bony matrix o ) ( - .mononuclear phagocyte system

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o " - : osteoclasts - osteoclast " . . , )+ (H . , , : ) collagenase (.

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: Osteogenesis: Woven bone Immature bone .Primary bone Osteogenesis . spongy .woven bone " ) ( lacunae of osteocytes ") "woven network ( . . remodeling - .lamellar bone 41 sutures , . , . : Lamellar bone Mature bone .Secondary bone -.woven bone )( ) (. ) (. . 41 woven bone , 41 . =) lamella, ( 2 . " .

Trabecular bone may be either woven or lamellar Compact bone is always lamellar

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mature compact bone "" : 1. ): Osteons ( Haversian systems o ) (Haversian system , 02-4 lamella ) ( .Haversian canal o 011-02 . o anisotropic " -anisotropic . .

o ,cement line . , . o " ,tetracycline - .cement line 2 - cement lines )5-4 (. o , Haversian canal . o - Haversians canals - ,periosteum .Volkmann's canals . - Haversian canals - .Volkman's canals 41

Lamellar boneOsteons Outer circumferential lamellae

Inner circumferential lamellae

Interstitial system

Endosteum

Volkmans canal

Haversian canal There are 3 lamellar arrangements in compact bone: 1. Osteons (Haversian Systems) 2. Circumferential lamella (outer, inner) 3. Interstitial systems: in between osteons

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2. : Circumferential Systems o - periosteum .outer circumferential lamellae o - endosteum .inner circumferential lamellae o Sharpey's fibers perforating fibers - periosteum - ) outer circumferential lameelae (. 3. :Interstitial systems o remodeling . o- interstitial systems .remodeling o - - .central Haversian canal

Interstitial System

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: Remodeling Osteoclasts - .resorbtion cavities Haversians canals - . osteoblasts - . , .interstitial systems - .

Bone multicellular unit (BMU)

Activation

Resorption

Reversal

Formation

Bone is continually undergoing change and the dynamic remodelling processes involve coordination between several bone types. These are sometimes described as bone multicellular units. These are regulated by interaction of several endocrine factors

Remodeling of bone leading from woven to lamellar bone

During remodelling of bone there is erosion of osteons by osteoclasts that results in connecting resorption cavities from adjacent osteons. When sufficient resorption has occurred, osteoblasts appear in the resorption cavities and start building a new generation of osteons. The remnants of earlier osteons are seen as interstitial systems.

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:Trabecular bone - .spongy bone - .woven bone / - spongy bone . ) spicules( . , )(. " - endosteum .

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: Osteogenesis : -2 : osteogenesis 1. .Intramembranous ossification , -. 2. " .Endochondral ossification , . **-2 " ) primary (woven ).(trabecular : Intramembranous ossification ) (flat bones . : 1.

mesenchyme cells . 2. . 3. fine collagen fibrils ) ' ,(gel-like .intercellular spaces 4. ) osteoblasts (. .prebone 5. .

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Intramembranous ossification

Early stages

Advanced stages

.Intramembanous ossification occurs mainly in pre-natal life Flat bones, such as those of the calvarium, develop by intramembranous ossification directly from connective tissue

: o )( . o Osteoblasts . o osteocytes . o osteoclasts . o . o - periosteum .

Intramembranous ossification

2, mesenchyme 3, blood vessel 4, bone matrix 5, osteoblasts 6, osteoclast

Developing calvarium in embryo

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: Endochondral ossification . : 1. hyaline cartilage model perichondrium ) (. 2. woven bone periosteal colar central shaft . 3. : Primary (diaphyseal) center of ossification o chondrocytes ) primary center of ossification ( ) ( . o- ECM -chondrocytes . o mesenchyme-like cells- periosteum . o osteoblast - primary bone .

4. bone marrow cavity osteoclastic activity - .primary spongy bone ) (. metaphysic" .growth plates 22

5. - chondrocytes . - :chondrocytes

. : resting zone .

. )( : zone of proliferation , .

. : zone of hypertrophy Chondrocytes .

. : zone of calcification - .chondrocytes

. : zone of ossification osteoblasts " .

. : primary spongiosa remodeling" .Osteclastic activity ** ) ( endochondrial ossification -remodeling diaphyseal bone marrow cavity

- .primary spongy bone

Growth plate of long boneResting zone Zone of proliferation

Zone of chondrocytes

Zone of hypertrophy and calcified cartilage Zone of and Primary Spongiosa formation The cartilage matrix is stained with alcian blue. The bone develops on the .remains of the calcified cartilage

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: Secondary (epiphyseal) center of ossification .6 , epiphyses o - , .chondrocytes " trabecular bone - osteoblasts o ..

: Clusure of the epiphyses 7. . 71-41 .

Endochondral ossificationA-F: Stages take place in the pre-natal life G-I: Stages take place during childhood and adolescence J: Adult bone

A - Cartilage anlagen B- Cartilage envelops by a Periosteal / peichondral layer C Calcified cartilage envelops by a Periosteal layer D invasion of blood vessels into the growing bone

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: 2 : bone trabeculae 1. . 2. . " . " " osteoblastic activity - , Periosteum " - osteoclast ) (. . remodeling . "" osteoporosis .

Osteoblasts, osteoid and matrix vesicles

Matrix vesicles

osteoid

Calcified matrix

.)The matrix secreted by osteoblasts is at first non-calcified (osteoid or prebone Processes of osteoblasts are nipped off to form membrane-bound matrix vesicles. Calcification processes occur on these matrix vesicles resulting in .deposition of hydroxyapatite crystals and mineralization of the matrix

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Normal bones

Osteoporotic bones

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: Bone fracture & repair brittle . . : 1. - periosteum- endosteum . 2. fibrous cartilage , fibrocartilaginous callus . 3. osteoclasts .bony callus of primary bone 4. remodeling ).secondary bone (lamellar

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: Synovial joints " . : Fibrous capsule - ) Diarthrosis ( ligament - periosteum 2 . : Synovial membrane synovial membrane .synovial fold . fat deposits . fibrous-like cells .synovial fluid : Synovial fluid hyaluronic acid . . .

** osteoarthritis .

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: ) .(remodeling . 3 Calcium homeostasis : 1. : Parathyroid hormone " - osteoclasts bone .resorption 2. : Calcitonin . - calcitonin - .osteoporosis 3. 3: Vitamin D 3 D . - .rickets

Growth factors and boneAll stages of bone development and growth are tightly regulated by a large complex system of .systemic and local growth factors Homeostatic mechanisms of bone physiology .differ according age, gender and growth phase :It is convenient to classify these stages as Fetal Neonatal Juvenile Adult Senile

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Endocrine regulation of boneMajor systemic hormones involved in skeletal growth and homeostasis include:Calcium-regulating hormonesParathyroid hormone Calcitonin, Vitamin D3

Growth regulating hormonesGrowth Hormone Insulin Glucocorticoids Thyroid Hormones (T3, T4)

Sex hormones Androgens Estrogens

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