Histogenesis of Bone

Alya Putri Khairani / 130110110220 /

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HISTOLOGY
Bone is a specialized connective tissue composed of calcified intercellular material, the bone matrix, and three
cell types:

Osteocytes, which are found in cavities (lacunae) between layers (lamellae) of bone matrix

Osteoblasts, which synthesize the organic components of the matrix

Osteoclasts, which are multi-nucleated giant cells involved in the resorption and remodeling of bone tissue.

Osteoblast

Responsible for the synthesis of the organic components of bone matrix, consisting of type I collagen fibers,
Proteoglycans, and several Glycoproteins including Osteonectin

Located exclusively at the surfaces of bone matrix, usually side by side in a layer somewhat resembling a
simple epithelium

When they are actively engaged in matrix synthesis, osteoblasts have a cuboidal to columnar shape and
basophilic cytoplasm. When their synthesizing activity declines, they flatten and cytoplasmic basophilia is
reduced

Osteoblast activity is stimulated by Parathyroid hormone (PTH)

Matrix components are secreted at the cell surface in contact with older bone matrix, producing a layer of new
(but not yet calcified) material called Osteoid between the osteoblast layer and the bone formed earlier
Osteocytes

Individual Osteoblasts are gradually surrounded by their own secretion and become Osteocytes enclosed
singly within spaces called Lacunae

In the transition from osteoblasts to osteocytes the cells extend many long cytoplasmic processes, which also
become surrounded by calcifying matrix

An Osteocyte and its processes occupy each Lacuna and the Canaliculi radiating from it
Osteoclasts

Large size and multinucleated condition of Osteoclasts is due to their origin

from the fusion of bone marrow-derived cells

In areas of bone undergoing resorption, osteoclasts lie within enzymatically

etched depressions or crypts in the matrix known as Resorption Bays

Osteoclast secretes Collagenase and other enzymes and pumps protons,

forming an acidic environment locally for dissolving Hydroxyapatite and
promoting the localized digestion of Collagen

In active osteoclasts, the surface against the bone matrix is folded into
irregular projections, which form Ruffled Border. Surrounding the ruffled
border is a clear cytoplasmic zone rich in actin filaments which is the site of
adhesion to the bone matrix. This circumferential adhesion zone creates a
microenvironment between the osteoclast and the matrix in which bone
resorption occurs

Activated by PTH produce a cytokine called Osteoclast Stimulating Factor

Osteoclasts also have receptors for Calcitonin. Thus, activity of these cells is coordinated and both are
essential in bone remodeling

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Bone Matrix
Inorganic material represents about 50% of the dry weight of bone matrix (Hydroxyapatite, Bicarbonate, Citrate,
Magnesium, Potassium, Sodium)

HISTOGENESIS
Bone primarily develops in two types of connective tissue, Mesenchyme and Cartilage, but can also develop in
other connective tissues. Like cartilage, bone consists of cells and an organic intercellular substance-the Bone
Matrix-that comprises collagen fibrils embedded in an amorphous component. Studies of the cellular and
molecular events during embryonic bone formation suggest that Osteogenesis and Chondrogenesis are
programmed early in development and are independent events under the influence of vascular events
Osteogenesis
Bone can be formed initially by either of two ways:

Intramembranous Ossification
In which Osteoblasts differentiate directly from Mesenchyme and begin secreting Osteoid

Endochondral Ossification
In which the matrix of preexisting hyaline cartilage is eroded and replaced by osteoblasts producing
osteoid
In both processes, the bone tissue that appears first is primary or woven. Primary bone is a temporary and is
soon replaced by the definitive secondary lamellar bone. During bone growth, areas of primary bone, areas of
resorption, and areas of secondary bone all appear side by side
(1) Intramembranous Ossification
Intramembranous ossification, by which most flat bones are produced, is so called because it takes place within
condensations of embryonic mesenchymal tissue. In the mesenchymal condensation layer or "membrane," the
starting point for bone formation is called an ossification center
1) The process begins when groups of Mesenchymal cells differentiate into Osteoblasts
2) Osteoblasts produce Osteoid matrix and calcification follows, resulting in the encapsulation of some
Osteoblasts, which then become Osteocytes
3) These islands of developing bone form walls that delineate elongated cavities containing capillaries, bone
marrow cells, and undifferentiated cells
4) Several such groups arise almost simultaneously at the ossification center, and their fusion between the
walls gives the bone a spongy appearance
5) The connective tissue that remains among the bone walls is penetrated by growing blood vessels and
additional undifferentiated mesenchymal cells, giving rise to the bone marrow
6) The ossification centers of a bone grow radially and finally fuse together, replacing the original connective
tissue

(2) Endochondral Ossification

Takes place within a piece of hyaline cartilage whose shape resembles a small version, or model, of the bone to
be formed. This type of ossification is principally responsible for the formation of short and long bones
1) Initially, the first bone tissue appears as a collar surrounding the diaphysis of the cartilage model
2) This Bone Collar is produced by local Osteoblast activity within the surrounding Perichondrium

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Alya Putri Khairani / 130110110220 /

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The collar now impedes diffusion of oxygen and nutrients into the underlying cartilage, promoting
degenerative changes there
The Chondrocytes begin to produce Alkaline Phosphatase and swell up (Hypertrophy), enlarging their
lacunae
These changes both compress the matrix into narrower Trabeculae and lead to calcification in these
structures
Death of the Chondrocytes results in a porous three-dimensional structure formed by the remnants of the
calcified cartilage matrix
Blood vessels from the former Perichondrium now the Periosteum penetrate through the bone collar
previously perforated by Osteoclasts, bringing Osteoprogenitor cells to the porous central region
Next, Osteoblasts adhere to the calcified cartilage matrix and produce continuous layers of primary bone
that surround the Cartilaginous matrix remnant
At this stage, the calcified cartilage appears Basophilic, and the primary bone is Eosinophilic. This process
in the diaphysis forms the Primary Ossification center
Secondary ossification centers appear slightly later at the epiphyses of the cartilage model and
develop in a similar manner. During their expansion and remodeling, the primary and secondary
ossification centers produce cavities that are gradually filled with bone marrow

In the secondary ossification centers, cartilage remains in two regions:

Articular cartilage, which persists throughout adult life and does not contribute to bone growth in length
Epiphyseal cartilage, which connects each Epiphysis to the Diaphysis

A plate of Epiphyseal cartilage is divided into five zones, starting from the Epiphyseal side of cartilage:
1.

The Resting zone consists of hyaline cartilage with typical

chondrocytes.

2.

In the Proliferative zone, chondrocytes begin to divide

rapidly and form columns of stacked cells parallel to the
long axis of the bone.

3.

The Hypertrophic Cartilage zone contains swollen

chondrocytes whose cytoplasm has accumulated glycogen.
Hypertrophy compresses the matrix into thin septa
between the chondrocytes.

Chondrogenesis
4.
In the Calcified cartilage zone, loss of the chondrocytes
Cartilage develops from mesenchyme and first appears in embryos during the fifth week. In areas where cartilage
is to develop, the Mesenchyme condenses to form Chondrification Centers. The Mesenchymal cells differentiate

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into Chondroblasts that secrete collagenous fibrils and the ground substance (extracellular matrix).
Subsequently, collagenous and/or elastic fibers are deposited in the intercellular substance or matrix. Three types
of cartilage are distinguished according to the type of matrix that is formed:

Hyaline cartilage, the most widely distributed type (e.g., in joints)

Fibrocartilage (e.g., in intervertebral discs)

Elastic cartilage (e.g., in auricle of ear)

References
Junqueiras Basdic Histoloy 12th Edition
Moore The Developing Human
Langman Medical Embryology

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Periosteum & Endosteum

External and internal surfaces of bone are covered by layers of bone-forming cells and vascularized connective
tissue called Periosteum and Endosteum.

Periosteum

Consists of a dense fibrous outer layer of collagen bundles and fibroblasts

Bundles of periosteal collagen fibers, called Perforating (or Sharpey's) fibers, penetrate the bone
matrix, binding the Periosteum to bone

The innermost cellular layer of the periosteum contains Mesenchymal stem cells called
Osteoprogenitor cells, with the potential to divide by mitosis and differentiate into osteoblasts

Osteoprogenitor cells play a prominent role in bone growth and repair

Endosteum

A single very thin layer of connective tissue, containing flattened Osteoprogenitor cells and Osteoblasts

Covers the small spicules or Trabeculae of bone that project into these cavities

Considerably thinner than the periosteum

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The principal functions of Periosteum and Endosteum are nutrition of osseous tissue and provision of a continuous
supply of new Osteoblasts for repair or growth of bone

TYPES OF BONES

Gross observation of bone in cross section shows dense areas generally without cavitiescorresponding to
Compact Boneand areas with numerous interconnecting cavitiescorresponding to Cancellous (spongy)
Bone
Microscopic examination of bone shows two types: immature Primary bone and mature Secondary bone:

Primary Bone Tissue

Primary bone is the first bone tissue to appear in embryonic development and in fracture repair. It is
characterized by random disposition of fine collagen fibers and is therefore often called Woven Bone. Other
characteristics of primary bone tissue are a lower mineral content (it is more easily penetrated by x-rays) and a
higher proportion of Osteocytes than that in secondary bones

Secondary Bone Tissue

Secondary bone tissue is the type usually found in adults. It characteristically shows multiple layers of calcified
matrix (each 37 m thick) and is often referred to as Lamellar Bone. Each complex of concentric bony
lamellae surrounding a small canal containing blood vessels, nerves, and loose connective tissue is called an
Osteon (formerly known as an Haversian system). Lacunae with Osteocytes are found between the
Lamellae, interconnected by Canaliculi which allow all cells to be in contact with the source of nutrients and
oxygen in the osteonic canal. The outer boundary of each Osteon is a more collagen-rich layer called the
Cement Line