The Importance Of The Resting Zone In The Epiphyseal Growth Plate (Important)

Me: My collaborator in the project found a very interesting article that shows just how critical the resting zone is in the development of the growth plate itself which I had discovered previously in my searching. I wanted to bring to light the discovery because it shows just which elements in the growth mechanism are the most critical, which must be either preserved or regenerated for longitudinal increase to occur.

Note: As always I am using PubMed and reading just the abstract. The Full Text for the article is either not available or I just didn’t want to expend the energy to do a massive search to find the full article.

1st paper: This article shows just how important the resting zone is to the overall entire growth plate. if you remove the proliferative and hypertrophic zones, apparently adolescent rabbit growth place of the distal ulnar can regrow back in most cases within just 1 week. If you take the growth plates and put them sideways next to the proliferative layer, the chondrocytes in the proliferative layer starts to align themselves in alignment with the resting zone chondrocytes. This also stops the ability of the chondrocytes in the proliferative layer from turning hypertrophic. this suggest the resting zone might have some form of orientation growht factor involved.

2nd paper: This article shows that researchers have been hypothesizing that the real cause of growth plate senescence if because the chondrocytes in the resting zone have a finite proliferative capacity that is gradually depleted. With the rabbits, they saw that the proliferation rate and the chondrocyte density in resting zones decreased with age. Gluccocorticoids and dexamethasone treatment decreased the proliferative rate of the chondrocytes which helped conserve their proliferative capacity for later. They slowed the senescence of growth plates and slowed the depletion of the number of chondrocytes in the resting zone. They also foun that estradiol cypionate treatment slowed resting zone chondrocyte proliferation

The Implications (READ THIS!): The first article shows how important the resting zone is to the overall growth plate. As long as you have the resting zone, you can create all of the rest of layers. The 2nd article make me understand at a still superficial level that apparently the puberty we go through is just estrogen telling the resting zone chondorcytes to proliferate faster, which means rate of loss>rate of growth. as long as that happens, the proliferation and subsequent hypertrophy and apoptosis is the explanation behind the jump in rate of growth or height increase we see in kids going through puberty and the growth spurts. However, the growth spurts do come at a cost, especially the growth spurt associated with puberty. The estrogen has pushed the rate of loss over a limit where the rate of growth is not enough to stave off the loss of the number of chondrocytes seen in the resting zone.

If we remember the cases seen of the 3 men who had mutations in their estrogen receptors, we remember that for 2 of the men, they still had open growth plates with cartilage even in their 30s. This shows that as long as estrogen doesn’t come along to accelerate the rate of decrease in the number of chondrocytes in the resitng zone, the rate of proliferation thus rate of increase of chondrocytes in the resting zone is probably (and i am making a big leap of faith here) self-sustaining, which will not ever drop the number of chondrocytes around. What we could do then to create growth spurts but never loss all of the chondrocytes is to create a way to inhibit and promote estrogen release alternatively where the loss of chondrocytes can be made up for by inhibiting estrogen affects afterwards. 

A device can be build that can specifically block estrogen ligands from reaching their receptors on the growth plate in a pulsing, sinusoidal fashion to use the feedback mechanism of the two rates themselves to cause multiple growth spurts throughout an adolescent’s growth and development!

source link HERE. and from source link 2 HERE. both are PubMed Articles.


Endocrinology. 2002 May;143(5):1851-7.

The role of the resting zone in growth plate chondrogenesis.

Abad V, Meyers JL, Weise M, Gafni RI, Barnes KM, Nilsson O, Bacher JD, Baron J.

Source

Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive MSC 1862, Bethesda, MD 20892, USA.

Abstract

In mammals, growth of long bones occurs at the growth plate, a cartilage structure that contains three principal layers: the resting, proliferative, and hypertrophic zones. The function of the resting zone is not well understood. We removed the proliferative and hypertrophic zones from the rabbit distal ulnar growth plate in vivo, leaving only the resting zone. Within 1 wk, a complete proliferative and hypertrophic zone often regenerated. Next, we manipulated growth plates in vivo to place resting zone cartilage ectopically alongside the proliferative columns. Ectopic resting zone cartilage induced a 90-degree shift in the orientation of nearby proliferative zone chondrocytes and seemed to inhibit their hypertrophic differentiation. Our findings suggest that resting zone cartilage makes important contributions to endochondral bone formation at the growth plate: 1) it contains stem-like cells that give rise to clones of proliferative chondrocytes; 2) it produces a growth plate-orienting factor, a morphogen, that directs the alignment of the proliferative clones into columns parallel to the long axis of the bone; and 3) it may also produce a morphogen that inhibits terminal differentiation of nearby proliferative zone chondrocytes and thus may be partially responsible for the organization of the growth plate into distinct zones of proliferation and hypertrophy.

PMID: 11956168         [PubMed – indexed for MEDLINE] 

J Endocrinol. 2006 Apr;189(1):27-36.

Depletion of resting zone chondrocytes during growth plate senescence.

Schrier L, Ferns SP, Barnes KM, Emons JA, Newman EI, Nilsson O, Baron J.

Source

Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Drive, MSC 1103, Bethesda, Maryland 20892, USA.

Abstract

With age, the growth plate undergoes senescent changes that cause linear bone growth to slow and finally cease. Based on previous indirect evidence, we hypothesized that this senescent decline occurs because growth plate stem-like cells, located in the resting zone, have a finite proliferative capacity that is gradually depleted. Consistent with this hypothesis, we found that the proliferation rate in rabbit resting zone chondrocytes (assessed by continuous 5-bromo-2′-deoxy-uridine labeling) decreases with age, as does the number of resting zone chondrocytes per area of growth plate. Glucocorticoid excess slows growth plate senescence. To explain this effect, we hypothesized that glucocorticoid inhibits resting zone chondrocyte proliferation, thus conserving their proliferative capacity. Consistent with this hypothesis, we found that dexamethasone treatment decreased the proliferation rate of rabbit resting zone chondrocytes and slowed the numerical depletion of these cells. Estrogen is known to accelerate growth plate senescence. However, we found that estradiol cypionate treatment slowed resting zone chondrocyte proliferation. Our findings support the hypotheses that growth plate senescence is caused by qualitative and quantitative depletion of stem-like cells in the resting zone and that growth-inhibiting conditions, such as glucocorticoid excess, slow senescence by slowing resting zone chondrocyte proliferation and slowing the numerical depletion of these cells, thereby conserving the proliferative capacity of the growth plate. We speculate that estrogen might accelerate senescence by a proliferation-independent mechanism, or by increasing the loss of proliferative capacity per cell cycle.

PMID:   16614378          [PubMed – indexed for MEDLINE] 

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