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Bone Bone is the main constituent of the adult skeleton. It is a skeletal connective tissue specialized for support and protection. Bone tissue is rich in blood supply, i.e. highly vascular tissue. Moreover, bone is a type of connective tissue but with calcified matrix. Functions: - It supports and protects the more fragile tissues and organs. - Harbors hematopoietic tissue (bone marrow). - Forms a system of levers and pulleys that multiply and focus the contractile forces of muscle. - The bone matrix function as an important storage site for calcium and other essential minerals. Types of Bone Tissue:

- Regular (long) or compact bone. - Irregular (flat) or spongy bone.

Parts of Long Bones: Most bones of the arms and legs (eg. the femur) are termed long bones. The different parts in bone are:- The diaphysis is the shaft of a long bone, - The epiphysis is its bulbous end. In adults, the diaphysis is cylindric with walls of compact bone and a central marrow cavity lined with endosteum. The epiphyses contains mostly spongy bone. Where bones contact other bones to form movable joints, their surfaces are covered by articular (Hyaline) cartilage.

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Surfaces: - The outer surfaces of bones are covered by two layers of connective tissue, the periosteum. The outer or fibrous layer is formed of dense connective tissue; the inner or osteogenic layer is formed of loose tissue containing bone cell precursors. - Sharpey's fibers are periosteal collagen fibers (nail shape) that penetrate bone matrix and anchor the periosteum to the bone. - The internal surfaces of bones are covered by a thin, condensed reticular connective tissue (endosteum) that contain bone and blood cell precursors. The endosteum lines the marrow cavity and sends extensions into the haversian canals. Composition: Bone tissue composed of cells (osteocytes, osteoblasts. and osteoclasts), fibers (type I collagen), and ground substance containing abundant mineral salts. It differs from other connective tissues primarily in having large quantities of inorganic salts in its matrix, accounting for its hardness. Structure of bone: As other connective tissues, bone is formed of:- Cells:

Osteogeneic cells,

Osteoblasts,

Osteocytes,

Osteoclasts.

- Matrix: organic and non-organic parts. - Fibers: collagen type I fibers.

Bone cells 1- Osteogenic (Osteoprogenitor) cells 

They are mesenchymal stem cells found in the periosteum and endosteum.

They are small spindle-shaped cells with pale cytoplasm and ovoid nuclei.

Two types are distinguishable by the electron microscope: one can differentiate into osteoblasts, and the other into osteoclasts.

Osteoblast precursors derive from embryonic mesenchyme and have sparse RER and Golgi complexes.

Osteoclast precursors derive from blood monocytes and have abundant free ribosomes and mitochondria. 2


2- Osteoblasts: 

They are bone forming cells, found in the growing surface of the bone (in the periosteum and endosteum) they form one-cell-thick sheets.

They are dividing cells that synthesize the organic components of bone matrix.

They are large rounded or cuboidal cells, with deep basophilic cytoplasm, welldeveloped RER and Golgi; and eccentric nucleus.

They synthesize and secrete all the organic components of bone matrix and may be involved in bone mineralization.

Once surrounded by matrix, osteoblasts are considered mature and called osteocytes.

3- Osteocytes 

The cells are branched, smaller than osteoblasts, and not divide.

They are terminally differentiated bone (mature) cells found in cavities in the bone matrix called lacunae, and their processes (branches) extend into canaliculi in the classified matrix.

Osteocytes are isolated from one another by an impermeable bone matrix and contact one another at the tips of their filopodia, often through gap junctions.

Osteocytes recently derived from osteoblasts are located near bone surfaces in rounded lacunae; older cells are found farther from the surface in flattened lacunae.

They maintain bone matrix.

The death of osteocytes results in bone breakdown, or resorption.

EM of relatively quiescent osteocyte (left) with cytoplasmic processes extend within canaliculi. And formative osteocyte (right) showing Golgi body (G), rER, and collagen fibers (arrows).

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4- Osteoclasts 

Osteoclasts are bone-resorbing cells that lie on bony surfaces in shallow depressions called Hawship's lacunae.

Osteoclasts are large multinucleated cells (~ 50

nuclei),

containing

with

acidophilic

abundant

cytoplasm

lysosomes

and

mitochondria and well developed Golgi complex; and brush border (Ruffled border) of plasma-membrane facing the bone marrow. 

They are derive from the fusion of blood monocyte derivatives and are considered components of the mononuclear phagocyte system.

The cells release acid, collagenase, and other lytic enzymes into the compartments; these break down bone matrix and release minerals, a process called bone resorption,

Bone matrix. Bone matrix contains organic components (osteoid), and inorganic components (bone mineral). The organic components constitutes about 50% of bone volume and 25% of bone weight. It is composed of type I collagen fibers and unmineralized ground substance, which is composed of proteins, carbohydrates, and small amounts of proteoglycans and lipids. The inorganic components (bone mineral) makes up about 50% of bone volume and 75% of bone weight. It is composed of calcium and phosphate, with some bicarbonate, citrate, magnesium and potassium and trace amounts of other metals.

Compact Bone 1- Periosteum: covering the long bone, and formed of two layers:- Outer fibrous layer of collagen fibers. - Inner cellular layer of osteogenic cells and osteoblasts. 2- Endosteum: a cellular layer lining the bone cavities, and formed of osteogenic cells and osteoblasts.

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3- Haversian system (osteon):- Bone lamellae are arranged concentrically around the blood vessels. The bone lamellae are formed of osteocytes inside lacunae and canaliculi embedded in calcified matrix. 4- Volkmann`s Canals:- They are transverse canals connecting blood vessels in the Haversian canals to each other and to those in the periosteum and in marrow cavities. 5- External circumferential lamellae. 6- Internal circumferential lamellae. 7- Interstitial lamellae.

Diagrammatic illustration of a section of compact bone showing the arrangement of osteocytes around Haversian canal to form the Osteon.

Spongy or cancellous bone -

Spongy bone forms a fine 3-dimensional lattice with many bony cavities, with branching and anastomosing slips of bone between the cavities, called trabeculae.

-

Spongy bone is found at the core of the epiphyses of mature long bones, at the core of short bones, and between the thick plates, or tables, of the flat bones of the skull, where it is called the diploii.

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Macroscopic and microscopic characters of Spongy or Cancellous bone, where multiple bone cavities filled with bone marrow.

Ossification (Bone formation) Bone is formed from mesenchymal embryonic tissue by two ways:-

Intra-membranous ossification; takes place in irregular bone.

-

Endochondral ossification; takes place in regular, or long bone.

1- Intra-membranous ossification: -

Some changes appeared at the site of ossification (ossification center) in the form of; increased the vascularity, condensation of mesenchymal cells.

-

Mesenchymal cells divide, proliferate, and differentiate into osteogenic cells.

-

Osteogenic cells more differentiate into osteoblasts; which synthesize the organic component of bone matrix (collagen, glycoprotein).

-

Also, osteoblasts secrete alkaline phosphatase enzyme which stimulate calcium salts deposition in the matrix and around the cells, i.e. the matrix become calcified.

-

The bone matrix grows in the membrane, and the vascular tissues that fills the spaces of spongy bone differentiate into hematopoietic tissue (bone marrow).

-

A layer of vascular mesenchyme is found on the outer and inner surfaces of the membrane forming periosteum.

-

The osteogenic stem cells in the periosteum differentiate to osteoblasts, which start to lay down or arrange bone lamellae (compact bone). 6


2- Endochondral Ossification It is best observed in long bone, where the cartilage model is replaced by bone. a- Cartilage model:- where embryonic mesenchymal cells are condensed in the shape of future bone. Then the cells differentiated to chondroblasts, chondrocytes, and cartilage matrix. b- Primary centers of ossification:- During late embryonic and early fetal periods, some changes have been developed -

Chondrocytes at the meddle of cartilage model enlarged, and calcium salts become to deposit around the lacunae.

-

Chondrocytes die due to prevention of nutrient diffusion through the calcified matrix, leaving empty spaces.

-

The perichondrium becomes highly vascular and active and changed to periosteum, where the inner vascular osteogenic cells differentiate to osteoblasts.

-

The osteoblasts start to lay down a collar of compact bone around the shaft called subperiosteal collar of bone.

-

The periosteum forms a periosteal bud, which is consists of; capillaries, osteoclasts, and osteoblasts.

-

The vascular bud invades the subperiosteal bone by osteoclasts, enters and occupies the empty spaces left after death of chondrocytes.

-

The thin wall of the empty lacunae is broken down forming the primary bone marrow cavity.

-

As the periosteal bud invades bone and cartilage, the osteoblasts arrange themselves along the marrow spaces and start to lay down bone matrix.

-

Marrow spaces joint together forming a central regular cavity in the middle of diaphysis.

The microscopic structure of the metaphyses of developing endochondral bones is characterized by 5 overlapping zones: -

The zone of resting cartilage is composed of typical hyaline cartilage and is farthest from the primary marrow cavity.

-

The zone of proliferation contains columns of flattened chondrocytes.

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-

In

the

zone

of

hypertrophy,

the

chondrocytes in the columns are enlarged and rounded. -

The zone of calcification, in H&E-stained sections, is characterized by a more basophilic

matrix.

There

is

often

a

significant overlap between zones 3 and 4, which are sometimes referred to as a single zone of hypertrophy and calcification. -

The zone of ossification borders directly on the

primary

characterized

marrow by

cavity.

intensely

It

is

acidophilic

osteoid, osteocytes within the bone matrix, and a monolayer of basophilic osteoblasts on the surface of the newly formed primary bone.

Bone growth Bones increase in size from birth into early adulthood. During this growth, the bone tissue is continuously remodeled. Growth occurs in 2 directions:

Growth in length of long bones is due to the proliferation of chondrocytes in the resting cartilage and in the zone of proliferation of the epiphyseal plates, under the influence of growth hormone.



Growth in girth occurs by proliferation and differentiation of osteoprogenitor cells in the inner layer of the periosteum and deposition of new ossified tissue on the outer surface of the bone.

Bone repair -

Bone fractures tear vessels in the periosteum, endosteum, and haversian and Volkmann's canals, causing local hemorrhage and clot formation between the broken ends of the bone.

-

The periosteum and endosteum provide macrophages to remove the clot and fibroblasts; to fill the gap with fibrous connective tissue. 8


-

Some of the connective tissue cells differentiate into chondrocytes, and the connective tissue eventually becomes a callus containing islands of fibro-cartilage and hyaline cartilage that serves as a model for bone formation.

-

The presence of cartilage in the callus is typical of endochondral bones (eg, long bones), whereas flat membrane bones (eg, the mandible) typically heal without cartilage formation.

-

Beginning in the subperiosteal region, the callus is gradually replaced by primary bone, which is subsequently remodeled and replaced by secondary bone.

-

The time required for complete healing depends on the site and extent of the injury and is longer in older people.

Diagrammatic illustration of bone healing model.

JOINTS Joints, or arthroses, are complex connective tissue structures that join individual bones to form the skeletal system. There are 2 main types:A. Synarthroses: These joints permit little or no movement. There are 3 subclasses: 1. Synostoses, the individual bones are fused and immobilized. Example: between the bones of the skull in elder people.

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2. Synchondroses, the individual bones are joined by cartilage and permit slight movement. Example: between the ribs and sternum; and in the pubic symphysis. 3. Syndesmoses, the individual bones are joined by dense connective tissue. These joints permit slight movement. Example: between the bones of the skull in younger people. B. Diarthroses: These are movable joints, like those between long bones. The articulating surfaces of bones are covered by articular (hyaline) cartilage, providing a smooth surface. The ends of the bones are joined by a 2-layered connective tissue joint capsule that seals off the articular cavity from the surrounding tissues. The outer, fibrous layer, which is composed of dense connective tissue, is continuous with the periosteum and supports the joint. The inner layer is the synovial membrane and contains 2 types of cell; (1) phagocytic A cells help clear the articular cavity of debris formed during friction between the articular cartilages. (2) B cells help produce the synovial fluid that fills the articular cavity. This fluid is viscous (owing to the presence of hyaluronic acid) and lubricates the articular cartilage to reduce friction. Some diarthroses (eg. the knee) are reinforced by ligaments inside or outside the articular cavity (eg, cruciate and collateral ligaments), and most are stabilized by surrounding muscles and tendons.

Diagrammatic illustration of joint structure

Diagrammatic illustration of the articular surface.

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