Bone Development Histology
What is the first step of endochondral ossification?
DEVELOPMENT OF FETAL CARTILAGE MODEL: Beginning again with mesenchyme, some mesenchymal cells aggregate and differentiate into chondroblasts. These chondroblasts secrete matrix, including type II collagen, and produce the hyaline cartilage model. This hyaline cartilage model is formed from mesenchyme where the bone is going to form and in a similar shape. This hyaline cartilage continues to grow by interstitial growth due to the activity of chondrocytes located in the lacunae and appositional growth due to the activity of chondroblasts at the surface. This hyaline cartilage model has a surrounding perichondrium.
What is the fifth step of endochondral ossification?
RETENTION OF HYALINE CARTILAGE AS THE ARTICULAR CARTILAGE AND THE EPIPHYSEAL PLATE: - Hyaline cartilage is retained on the ends of the model and becomes the articular cartilage for cushioning of bone ends participating in joints. - Additionally, the remnant of hyaline cartilage between the epiphysis and the flared portion of the diaphysis (known as the metaphysis) is retained as the epiphyseal plate, which will be responsible for the lengthwise growth of long bones.
What are the controls of bone remodeling?
TWO CONTROLS IMPACTING BONE REMODELING: (negative feedback loop, mechanical stresses and gravity) 1) Negative feedback loop for maintenance of calcium homeostasis (impacts when remodeling occurs): CALCITONIN & PARATHYROID HORMONE 2) Bone's response to mechanical stress and gravity (impacts where remodeling occurs) **You remodel 5-10% of your bone every year** - The negative feedback loop defines WHEN remodeling occurs. This negative feedback loop maintains the homeostasis of a certain amount of Ca2+ in the blood through the release of the hormones calcitonin and parathyroid hormone. Ca2+ is important in the blood as it is needed for many physiological processes. - The mechanical stresses placed on bones and gravity's pull on bones define WHERE remodeling occurs
What is the first zone of the epiphyseal plate and what occurs in that zone?
ZONE 1: RESTING OR RESERVE CARTILAGE - Again, this is the zone that is closest to epiphysis. - In this zone, you will see chondrocytes singularly or in very small groups. - Basically, nothing exceptional in going on in this zone; there is no active matrix production and no mitosis underway.
What is the second zone of the epiphyseal plate and what occurs in that zone?
ZONE 2: ZONE OF PROLIFERATION OR PROLIFERATING CARTILAGE - In this zone, cartilage cells (specifically chondrocytes in lacunae) are undergoing MITOSIS and are stacking up like coins in line with the long axis of the bone. - These stacks of cartilage cells that look like coins are isogenous groups. - These cells are also actively producing matrix. - With the division oriented in this direction (specifically along the long axis of the bone) and the matrix production - the epiphysis is pushed away from the diaphysis causing the bone to lengthen.
What is the third zone of the epiphyseal plate and what occurs in that zone?
ZONE 3: ZONE OF HYPERTROPHY OR HYPERTROPHIC CARTILAGE - In this zone, chondrocytes increase in size. In other words, they undergo hypertrophy. - During this process, the cytoplasm of the chondrocytes accumulates glycogen. - When the chondrocytes undergo hypertropy, the matrix is compressed/thinned due to the expansion of the cells.
What is the fourth zone of the epiphyseal plate and what occurs in that zone?
ZONE 4: ZONE OF CALCIFIED CARTILAGE - In this zone, the cartilage matrix begins to calcify through the formation of hydroxyapatite crystals. This calcified cartilage matrix stains basophilic. - Due to the calcified cartilage, the chondrocytes can no longer receive the nutrients they need via diffusion and they die.
What is the fifith zone of the epiphyseal plate and what occurs in that zone?
ZONE 5: ZONE OF OSSIFICATION (ZONE OF RESORPTION OR ZONE OF REMODELING) - This zone is in direct contact with marrow tissue, as it right next to the diaphysis. - In this zone, small blood vessels, blood cells, osteoprogenitor cells, and osteoclasts enter into the spaces previously occupied by the chondrocytes.- Bone (specifically primary/woven bone) is laid down by osteoblasts onto the calcified cartilage spicules that were left behind. Remember, bone stains eosinophic. - Eventually, much of this new bone and calcified cartilage will be eroded by the osteoclasts, so that secondary bone can be developed or to add space to the already existing medullary cavity.
How does the negative feedback loop regulate bone remodeling?
- If too much Ca2+is in blood , the parafollicular cells in the thyroid gland secrete calcitonin which inhibits osteoclasts and, therefore, bone resorption, as well as encourages calcium salt to be deposited into bone matrix as it transiently also increases osteoblast activity. These changes lower the elevated blood calcium levels by the removal of Ca2+ from the blood and its deposit into bone. - If too little Ca2+ is in blood, the parathyroid glands (which are multiple pea-sized glands on the posterior side of the thyroid gland) secrete parathyroid hormone (PTH) which does a number of things including stimulating osteoclasts to resorb bone. This resorption of bone releases Ca2+ from storage in the bone and it enters the blood. This raises low blood calcium levels back to normal levels.
How does bone growth (length) occur?
- The process to do so is basically endochondral ossification and occurs in the epiphyseal plate. - The epiphyseal plate is composed of hyaline cartilage that can be divided into different zones. The first zone (i.e., the zone of resting cartilage or reserve cartilage) is located next to the epiphysis, while the last zone (i.e., the zone of ossification or zone of resorption) is closest to the diaphysis.
What are the steps of intramembranous ossification?
1) DEVELOPMENT OF THE OSSIFICATION CENTER: Some of the elongated, pale-staining, mesenchymal cells cluster, differentiate into osteoprogenitor cells, and then become more rounded, while their cytoplasm changes from eosinophilic to basophilic. This basophilic change is due to changes in the cytoplasm including the addition of more rough endoplasmic reticulum. These cells have now differentiated into osteoblasts. This cluster of osteoblasts creates the ossification center as the osteoblasts secrete organic extracellular matrix known as osteoid. (2) CALCIFICATION: Calcium and other mineral salts are deposited around the framework of collagen fibers. Cells that are trapped in the calcifying osteoid are now called osteocytes and sit in lacunae. 3) WOVEN BONE AND PERISOTEUM DEVELOPMENT: What is being made here is primary bone (also known as woven bone or immature bone). This woven bone is produced in small irregularly shaped pieces or spicules that are increased in size by apposition growth (meaning growth along the surface). This growth allows the small patches of bone production to merge together to produce a labyrinth of woven bone. Then, the spaces between the bone spicules are infiltrated with embryonic blood vessels, which will differentiate into red bone marrow. Additionally, the mesenchyme at the periphery of the bone condenses and forms the periosteum. 4) REPLACEMENT OF WOVEN BONE: The woven bone is then replaced by lamellar bone, forming compact and spongy bone. Specifically, with flat bones, spongy bone will be formed between two layers of compact bone.
What is the second step of endochondral ossification?
BONE COLLAR FORMS AROUND DIAPHYSIS AND CARTILAGE OF SHAFT BEGINS TO CALCIFY: - The perichondrium near the mid-region of the cartilage model contains progenitor cells that differentiate no longer into chondroblasts, but instead into osteoblasts. Therefore, this perichondrium is now functionally a periosteum. The osteoblasts that are produced along the surface of the mid-region of the cartilage model secrete osteoid, which is subsequently calcified. This creates a bone collar around the mid-section of the hyaline cartilage model. This bone collar forms along the diaphyseal portion of the developing bone and is the first bone tissue that appears. - This bone collar begins to impede the diffusion of oxygen and nutrients into the underlying cartilage. This promotes changes. - The chondrocytes in the mid-region begin to accumulate glycogen, undergo hypertrophy (or, in other words, they swell up), and also produce alkaline phosphatase. These changes compress the matrix and signal the surrounding matrix to calcify. (Keep in Mind: Calcified cartilage is not the same as bone. For example, hyaline cartilage is composed primarily of type II collagen, while bone is composed of primarily type I collagen. With a H&E stain, calcified hyaline cartilage stains blue/purple, while newly formed bone stains pink/red.) - With the matrix calcified, the chondrocytes can no longer get the nutrients they need, as diffusion cannot take place through the calcified cartilage matrix. Therefore, the chondrocytes subsequently die. - Without the chondrocytes present, the matrix begins to break down. - As a result, a porous 3-D structure of calcified hyaline cartilage is created in the shaft or diaphyseal region.
How does bone growth (width)?
Bone increases diameter/width with appositional growth (growth along the surface) - at periosteal surface: osteoblasts secrete bone matrix - at endosteal surface of bone: osteoclasts breakdown bone matrix - However, you don't want to keep adding onto the outer surface of your bone without removing from the inner surface of the bone. Otherwise, your bones will become too thick and, therefore, too heavy for you to move. - Therefore, at the endosteal surface, osteoclasts will resorb or remove bone. - The rate of the activity of the osteoblasts at the periosteal layer should equal the rate of the activity of the osteoclasts at the endosteal layer to keep bones from becoming too heavy or too thin.
What is the third step of endochondral ossification?
DEVELOPMENT OF PRIMARY OSSIFICATION CENTER IN DIAPHYSIS: - Capillaries and osteoprogenitor cells from the new periosteum penetrate the bone collar and grow into the disintegrating calcified cartilage location inducing the creation of the primary ossification center. - These entering blood vessels into this open space at the core of the diaphysis are important for the development of the bone marrow for the medullary cavity. - Osteoprogenitor cells brought into the area differentiate into osteoblasts. These osteoblasts begin to deposit bone matrix against the remnants of the calcified cartilage. In other words, primary or woven bone is produced along the side of the remaining spicules of calcified cartilage. - Remember, the primary bone is eosinophilic and calcified cartilage is basophilic. The calcified cartilage will also be identifiable as it will be cell-less (in other words, it has no chondrocytes present). This is unlike the bone which will have cells (specifically osteocytes) in the lacunae. - Again, this primary ossification center is found in the diaphysis - while at this same time, hyaline cartilage remains in the ends (or epiphyses) of the developing bone.
What is the fourth step of endochondral ossification?
DEVELOPMENT OF SECONDARY OSSIFICATION CENTERS: - After birth, secondary ossification centers develop in a similar manner to that of the primary ossificaiton center in the diaphysis. However, these secondary ossification centers are located in the epiphyses. - Chondrocytes in the epiphyses undergoes hypertrophy, the cartilage matrix is compressed, the cartilage matrix calcifies, and the chondrocytes subsequently die - all of which opens up spaces between spicules of calcified cartilage. - Then, blood vessels and osteoprogenitor cells enter the spaces that have been opened up in the epiphyses and secondary ossification centers develop.
What is the sixth step of endochondral ossification?
EPIPHYSEAL PLATES OSSIFY AND FORM THE EPIPHYSEAL LINES: - At the end of puberty, which marks the end of growth in terms of height, hormone changes cause the epiphyseal cartilage to be replaced with bone forming the epiphyseal line. - The epiphyseal line, therefore, is the remnant of the last location of the epiphyseal plate.
Does the epiphyseal plate change width during the growth of an individual?
NO. the epiphyseal plate remains the same width during the growth of an individual - This means that cartilage growth must equal bone tissue replacement. - However, at epiphyseal plate closure - hormones signal for the end of chondrocyte division and bone replaces all of the cartilage. This produces the epiphyseal line. - In other words, the amount of new cartilage produced in the zone of proliferation needs to equal the activity in the zone of ossification OR the activity of the chondrocytes needs to equal the activity of the bone cells. - Over time as the bone lengthens, as the epiphysis is pushed further away from the diaphysis, it appears as if the chondrocytes are being chased by the bone cells. These chondrocytes proliferate and form new cartilage, which they then vacate, and the bone cells invade the previously occupied area. - However, at epiphyseal plate closure - hormones signal for the end of chondrocyte division and bone replaces all the cartilage. This produces the epiphyseal line. It is at this point, at epiphyseal plate closure, that the bone cells have "caught up" with the chondrocytes. *Chondrocytes RUN and osteocytes CHASE*
What is ossification? What are the two types of ossification?
Ossification: development of bone tissue; During ossification, primary bone (also known as woven bone or immature bone) will be produced first. However, that primary bone is only temporary, as it will be replaced through remodeling with secondary bone (also known as lamellar bone or mature bone). - Intramembranous Ossification: NO hyaline cartilage model presursor, mesenchyme --> bone; this process leads to the production of the flat bones of the skull and the bones of the face; This process begins to occur around the 8th week of gestation in humans - Endochondral Ossification: hyaline cartilage model precursor, mesenchyme --> hyaline cartilage --> bone; leads to the production of most short and long bones of the body; During embryonic development in humans, the first hyaline cartilage models are visible in the 6th week of gestation and ossification centers are present in all long bones of the limbs by the 12th week of gestation.
