3+ 4/2002 - Společnost pro pojivové tkáně

activity through expression of RANKL.
Osteoclastic regulation is assisted through
secretion by osteoblastic and other cells of
osteoprotegerin (OPG), a soluble decoy
receptor for RANKL.TGF beta appears to be
an essential cofactor for osteoclast formation.Thus
TGF beta not fully powerfully synergizes
with RANKL, but osteoclasts formation
is abolished by soluble TGF beta
receptors. TGF beta seems to act partly by
preventing the development of resistance to
OCL-induction that otherwise occurs when
precursors are incubated in M-CSF, and
opposes the ability of agents such as IFN
gama to induce alternative macrophagic lineages.TGF
beta also suppresses apoptosis in
osteoclasts.
Surprisingly, not only RANKL, but TNF
alfa can induce osteoclasts formation in
vitro, especially in the presence of TGF
beta. Thus TNF alfa can induce inflammatory/cytotoxical
makrophages of osteoclasts,
depending upon the presence opr absence
of cofactors such is interferons or TGF beta.
This suggest a model in which lineage is
activated by RANKL/TNF alfa, but determined
by cofactors.
TNF alfa enhances bone resorption by
several pathways. Not only induces RANKL
in osteoblastic cells and directly stimulate
osteoblastic differentation. Moreover, TNF
alfa strongly synergizes with RANKL, such
that minimale concentrations of TNF alfa
are sufficient to substantially augment osteoclast
activation. The extreme sensitivity of
osteoclasts to activation by TNF alfa suggest
that the most sensitive osteolytic response
of bone to TNF alfa is through activation of
existing osteoclasts, and the strong synergy
with RANKL provides a mechanism whereby
increased osteolysis can be achieved
without disturbance to the underlying pattern
of osteoclastic localisation.
134
VALIDATION OF A NEW AUTOMATED
IMUNOASSAY FOR MEASUREMENT
OF INTACT OSTEOCALCIN
W. J. Fassbender, B. Steinhauer, H. Stracke,
P. M. Schumm – Draeger, K.H. Usadel
I. University Clinic, Frankfurt/M Germany
III- University Clinic, Giessen , Germany
LOCOMOTOR SYSTEM vol. 9, 2002, No. 3+4
Bone turnover is assesssed indirectly by
measurement of biochemical markers of
bone turnover.
Osteocalcin, a 49 aminoacid protein is
a major noncollagenous protein of bone
matrix, synthesized by osteoblasts and
odontoblasts. Various assays exist for assesment
of osteocalcin and concentrations in
the same serum sample may vary enormously.
The used antibodies may recognize
intact osteocalcin anad/or circulating fragments
of osteocalcin.
We observed highly significant correlation
between both asssays for healthy persons
and also for patient samples. Very low
inter and intraaassay covariance as well as
highly significant linearity tested by seriál
dilutions were demonstrated.
The described automated intact osteocalcin
assay shows highly significant correlations
to the compared established IRMA
method. We conclude, that the here validated
IMMULITE assay is an useful test systém
for assesment of serum intact osteocalcin
giving valuable results in comparison to the
established non automated assay.