An Analysis Of The Epiphyseal Growth Plates Part I

This is the first in a series of posts where I really go deep in the study and analysis of the main body parts or body chemical signals that occur in the body in the natural height growth process. I know I have already talked about these topic extensively already but I have never focused completely on the topic I will get into. I will focus on the epiphyseal growth plates in this post.

First, a quick intro from Wikipedia (source HERE)


Epiphyseal plate

From Wikipedia, the free encyclopedia

The epiphyseal plate (or epiphysial platephysis, or growth plate) is a hyaline cartilage plate in the metaphysis at each end of a long bone. The plate is found in children and adolescents; in adults, who have stopped growing, the plate is replaced by an epiphyseal line.

Endochondral ossification is responsible for the initial bone development from cartilage in utero and infants and the longitudinal growth of long bones in the epiphyseal plate. The plate’s chondrocytes are under constant division by mitosis. These daughter cells stack facing the epiphysis while the older cells are pushed towards the diaphysis. As the older chondrocytes degenerate, osteoblasts ossify the remains to form new bone. In puberty increasing levels of estrogen, in both females and males, leads to increased apoptosis of chondrocytes in the epiphyseal plate. Depletion of chondrocytes due to apoptosis leads to less ossification and growth slows down and later stops when the entire cartilage have become replaced by bone, leaving only a thin epiphyseal scar which later disappears. Once the adult stage is reached, the only way to manipulate height is modifying bone length via distraction osteogenesis.

Role in bone elongation

The growth plate has a very specific morphology in having a zonal arrangement. The growth plate includes a relatively inactive reserve zone at the epiphyseal end, moving distally into a proliferative and then hypertrophic zone and ending with a band of ossifying cartilage (the metaphysis). A mnemonic for remembering the names of the epiphyseal plate growth zones is ” Real People Have Career Options,” standing for: Resting zone, Proliferative zone, Hypertrophic cartilage zone, Calcified cartilage zone, Ossification zone. The growth plate is clinically relevant in that it is often the primary site for infection, metastasis, fractures and the effects of endocrine bone disorders.


Me: So the growth plate is not just 1 layer of cartilage. There is actually 5 layers which start from the epiphysis of the long bone and goes in the metaphysis of the long bone. So the layering order is Epiphysis–>Resting zone–>Proliferative zone–> Hypertrophic zone–> Calcified zone–>Ossification Zone–>Metaphysis. 

The growth plates is made of mainly a type of cartilage called hyaline cartilage. The actual cartilage is an actual matrix of three main components, chondocytes, collagen, and proteoglycans. The cartilage’s cells is the chondrocyte. Chondrocytes are the cells that go through the process of mitosis and split into two same cells over and over again. The increased number of cells increases usually at a set rate, which is the real rate of long bone longitudinal growth aka rate of height increase or height growth. As the chondrocytes multiply and increase in number the old cells get pushed in in the metaphysis direction towards the hypertrophic cartilage zone. while the newly formed chondrocyte cells gets pushed to the epiphysis direction, towards the resting zone.

Let’s study further on using the Wikipedia article on Endochondral Ossification (located HERE)


Histology

During endochondral ossification, five distinct zones can be seen at the light-microscope level.

  1. Zone of resting cartilage. This zone contains normal, resting hyaline cartilage.
  2. Zone of proliferation / cell columns. In this zone, chondrocytes undergo rapid mitosis, forming distinctive looking stacks.
  3. Zone of maturation / hypertrophy. It is during this zone that the chondrocytes undergo hypertrophy (become enlarged). Chondrocytes contain large amounts of glycogen and begin to secrete alkaline phosphatase.
  4. Zone of calcification. In this zone, chondrocytes are either dying or dead, leaving cavities that will later become invaded by bone-forming cells. Chondrocytes here die when they can no longer receive nutrients or eliminate wastes via diffusion. This is because the calcified matrix is much less hydrated than hyaline cartilage.
  5. Zone of ossification. Osteoprogenitor cells invade the area and differentiate into osteoblasts, which elaborate matrix that becomes calcified on the surface of calcified cartilage. This is followed by resorption of the calcified cartilage/calcified bone complex.

Growth of the cartilage model

The cartilage model will grow in length by continuous cell division of chondrocytes, which is accompanied by further secretion of extracellular matrix. This is called interstitial growth. The process of appositional growth occurs when the cartilage model also grows in thickness due to the addition of more extracellular matrix on the peripheral cartilage surface, which is accompanied by new chondroblasts that develop from the perichondrium.

Primary center of ossification

The first site of ossification occurs in the primary center of ossification, which is in the middle of diaphysis (shaft). Then:
  • Formation of periosteum: The perichondrium becomes the periosteum. The periosteum contains a layer of undifferentiated cells (osteoprogenitor cells) which later become osteoblasts.
  • Formation of bone collar: The osteoblasts secrete osteoid against the shaft of the cartilage model (Appositional Growth). This serves as support for the new bone.
  • Calcification of matrix: Chondrocytes in the primary center of ossification begin to grow (hypertrophy). They stop secreting collagen and other proteoglycans and begin secreting alkaline phosphatase, an enzyme essential for mineral deposition. Then calcification of the matrix occurs and apoptosis of the hypertrophic chondrocytes occurs. This creates cavities within the bone. The exact mechanism of chondrocyte hypertrophy and apoptosis is currently unknown.
  • Invasion of periosteal bud: The hypertrophic chondrocytes (before apoptosis) secrete Vascular Endothelial Cell Growth Factor that induces the sprouting of blood vessels from the perichondrium. Blood vessels forming the periosteal bud invade the cavity left by the chondrocytes and branch in opposite directions along the length of the shaft. The blood vessels carry hemopoietic cells, osteoprogenitor cells and other cells inside the cavity. The hemopoietic cells will later form the bone marrow.
  • Formation of trabeculae: Osteoblasts, differentiated from the osteoprogenitor cells that entered the cavity via the periosteal bud, use the calcified matrix as a scaffold and begin to secrete osteoid, which forms the bonetrabecula. Osteoclasts, formed from macrophages, break down spongy bone to form the medullary (bone marrow) cavity.

Secondary center of ossification

About the time of birth, a secondary ossification center appears in each end (epiphysis) of long bones. Periosteal buds carry mesenchyme and blood vessels in and the process is similar to that occurring in a primary ossification center. The cartilage between the primary and secondary ossification centers is called the epiphyseal plate, and it continues to form new cartilage, which is replaced by bone, a process that results in an increase in length of the bone. Growth continues until the individual is about 26 years old or until the cartilage in the plate is replaced by bone. The point of union of the primary and secondary ossification centers is called the epiphyseal line.

Appositional bone growth

The growth in diameter of bones around the diaphysis occurs by deposition of bone beneath the periosteum. Osteoclasts in the interior cavity continue to degrade bone until its ultimate thickness is achieved, at which point the rate of formation on the outside and degradation from the inside is constant.

Me: It is important to understand what is hypertrophy (source)

Hypertrophy (from Greek ὑπέρ “excess” + τροφή “nourishment”) is the increase in the volume of an organ or tissue due to the enlargement of its component cells.

Me: I strongly suggest the reader who is not familiar with the physiology of the growth plate to read and understand the information  above. The most interesting thing stated on Wikipedia is that the mechanism for why or how the chondrocytes go through hypertrophy and apoptosis is still not known at this time. 

The life of a chondrocyte starts really from a the progenitor which is the mesenchymal stem cell. From source,…

Undifferentiated mesenchymal stem cell lose their process, proliferate and crowd together in a dense aggregate of chondrogenic cells(cartilage) at the center of chondrification. These condrogenic cells will then differentiate to chondroblasts which will then to synthesize the cartilage ECM(extra cellular matrix). Which consists of ground substance(proteoglycans, glycosaminoglycans for low osmotic potential) and fibers. The chondroblasts then trap themselves in a small space that is no longer in contact with the newly created matrix called lacunae which contain extracellular fluid. The chondroblast is now a chondrocyte, which is usually inactive but can still secrete and degrade matrix depending on the conditions. The majority of the cartilage that has been built has been synthesized from the chondroblast which are much more inactive at a late age (adult hood) compared to earlier years (pre-pubesence)

Me: When the newly formed chondrocyte is from mitosis of existing chondrocytes in the proliferate zone, they first get pushed to the resting zone. They release as waste the collagen and proteoglycan which forms the matrix of the hyaline cartilage. The stacking of the cells from the mitosis process of the proliferative zone seems to cause the original chondrocytes to get pushed away from the proliferative zone. into the hyper trophic zone where the cells stop releasing collagen or proteoglycan. secreting alkaline phosphatase, an enzyme essential for mineral deposition. Then calcification of the matrix occurs and apoptosis of the hypertrophic chondrocytes occurs. The reason for the chondrocytes apoptosis is believed because they have been pushed too far away from the nutrient rich blood vessel areas of the cartilage of the plate.

The cells have now been pushed to the calcification zone and the cells are either already dead or dying. This creates cavities within the bone which eventually gets filled up by the osteoblasts. The osteoblasts use the calcified matrix as a scaffold and begin to secrete osteoid, which forms the bonetrabecula. Osteoclasts, formed from macrophages, break down spongy bone to form the medullary (bone marrow) cavity.

From Duke Health, we learn that

1. On average, females are done growing around age 12 to 14, and boys around age 14 to 16.

2. Most children grow an average of two years after they have completed their pubertal growth spurt.

From a previous article I wrote about the different cartilages and when they close, it turns out the cartilage in our torso of the vertebrate do not completely ossify when the long bone’s growth plates fuse, at least by 2 years. So even if your X-rays from your doctor come back saying your growth plates are fused, they haven’t checked the cartilage in your vertebrate and your torso.

This means that Boys and Girls will actually stop increasing in by +4 years of what was stated above. So males stop increasing in height around the 18-20 year marks, while the Females stop increasing in height around the 16-18 year mark.

From the University of Pennsylvania website HERE….

It likewise grows and expands centrifugally in all directions, although much more slowly than did the primary center. As the distance between the growth plate and the epiphysis gradually decreases, the portion of the epiphysis that faces the growth plate closes and becomes sealed with condensed bone, termed the terminal bone plate or simply the bone plate.(78)Thereafter the epiphysis assumes a somewhat flattened hemispheric appearance and slowly fills out the remaining end of the long bone.

the growth plate may be divided anatomically into three components: a cartilaginous component, itself divided into various histologic zones; a bony component, or metaphysis; and a fibrous component surrounding the periphery of the plate comprising the groove of Ranvier and the perichondrial ring of LaCroix. How the growth plate synchronizes chondrogenesis with osteogenesis or interstitial cartilage growth with appositional bone growth at the same that it is growing in width, bearing load, and responding to local and systemic forces and factors is a fascinating phenomenon the key features of which are only beginning to be understood at the present time.

Me: What seems to be the big problem is that the process of human growth, or longitudinal lengthen increasing is not fully understood, but only at a very basic level. There is still a lot that researchers and scientists don’t understand. They know that the human body is going through two major processes at the same time. One is chondrogenesis or the creation and division of chondrocytes. At the same time, the process of osteogenesis (the creation and growth of bone) is occurring too right next to it making the entire process of going from the initial chondrocytes into the eventual bone component is done smoothly. 

[Note: This article post is turning out to be far longer and more deep in study than I expected so I decided to stop it right here and continue on the study of the growth plate in a later post. ]

One thought on “An Analysis Of The Epiphyseal Growth Plates Part I

  1. Nam Vu

    Hi, I’m studying this right now and I am hoping you can help me. Does longitudinal growth occur because 1) the epiphyseal plate is simply “pushing up” the epiphysis and leaving a “trail” of bone or 2) is a combination of this and epiphysis remodeling too?

    This figure seems to suggest #1: http://www.naturalheightgrowth.com/wp-content/uploads/2012/08/GrowthPlates.jpg
    While this figure suggests #2: http://o.quizlet.com/i/sjRSF-8zF-ifYcsrSAdYlw_m.jpg

    Thanks for your help.

    Reply

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