PADOVA STUDY CLUB

BONE TISSUE REMODELING 

I think we should reconsider the dynamics of bone/tissue
remodeling and how signal-proteins are involved in this process.

Referring to the current knowledge of bone/tissue
biology there are only a few facts that we know:

1. growth of tissue requires cell division

2. properties of the daughter cell need to be identical
to the mother cell, otherwise the resulting tissue would loose its original properties

3. these properties of a cell are in accordance with its
location and function (cornea, heart, bone, pancreas, liver, connective
tissue...) ,and are "frozen" within its DNA

4. during cell cycle the DNA doubles and thus ensures
the transfer of the properties

5. to initiate cell division especially during healing,
the cells need certain proteins, called cytokines of the injured cell, which
are being released by the content spill on the occasion of the injury

6. these cytokines need specific receptors on the
target cell to initiate its accelerated cell division

7. a cell of a different tissue does not provide these
specific receptors thus avoiding an increased cell division of a non-injured
tissue/cell, that doesn't need healing

8. in transplanting tissue pieces to a different
location even within an individual body, the target environment does not match
the receptor-system for the cytokines of the injured cells of the transplant
(the reason for kidney rejection)

9. in exchanging bone pieces from the hip, the mandible
or the maxilla, the miss-match of the receptors and the cytokines of the source
and the target environment leads to a stop of the cell cycle, ultimately of the
healing process

10. in accordance with its embryologic origin of the
neural crest tube (a very early stage of development) there are three different
bone types with different cytokine/receptor systems:

a. skull with the maxilla (forebrain)

b. mandible (midbrain)

c. skeleton (hindbrain)

11. there are numerous natural blocking membranes
which avoid unintentional mixing of tissue-specific signal-proteins like
cytokines: e.g. dura mater, pericardium, kidney capsule, pleura and so on

12. in bone this is the periosteum

13. the denudation of periosteum not only leads to
swelling because the fluid comes out (kind of 'leaking'), but also to the
development of a new blocking 'membrane', a new periosteum as a result of the competing
cytokines of the soft tissue and the bone.

14. an artificial blocking membrane inhibits this
competition.

In principle this is it. Of course it’s more
complicated than described here, only my humble list. For those who are
interested in further reading I may refer to the textbook of Bruce Alberts: The Molecular Biology Of The Cell, 4th
Ed., and with regard to the origin of the bone types to Helms, J.A. et al. and their review
article in Nature 423, 2003; abstract
available at Medline.

However, the role of the bone transplant is reduced to
being a space-holder. This piece will never be integrated as bone. In contrast
it will be disintegrated into resorbable components by means of MMP’s, other
enzymes and enzyme-catalysed addition of water (hydrolysis) as every biologic/synthetic
(TCP and HP) foreign substance will be. Depending on the amount of its volume this
process takes a more or less long time (app. 1-2 years).

As to your question for anything different: your first
intention was to place too big an implant into a too narrow bone. Instead of
trying to adjust the bone to the implant you may circumnavigate these futile surgical
attempts (imagine the effort of a hip bone transplant) and the disappointment
for you and your patient in switching to a different implant that fits into the
available bone in the first place.

Questions are welcome.

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