# CYTOKINES IN BONE

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 1991 · $114,173

## Abstract

A number of factors, which are thought to act predominantly as
local regulator of cellular function, have been shown to have
activity on bone cells or bone organ cultures.  These include IL-
1, TNF, gamma interferon, CSF, EGF, TGF alpha and TGF beta.

However, not all bone culture models respond identically to these
potential local regulators.  The responses of fetal long bone and
newborn calvaria cultures to EGF and TGF alpha differ.  In the
latter resorption stimulated by these growth factors is dependent
on prostaglandin synthesis while in the former it is not.  The
mechanisms underlying these differences are unknown.  Recently, I
have found that the addition of subresorptive concentrations of
IL-1 to the medium of fetal long bone cultures causes their
responses to EGF and TGF alpha to resembled those of newborn
calvaria cultures.  These results led me to examine whether bone
organ cultures spontaneously produce an IL-1 like factor because
differences in the rate of the production of such a factor could
explain some of the differences that exist between the response of
these two bone organ culture models.  I have now generated evidence
that both fetal long bone and newborn calvaria cultures produce IL-
1-like factors and that parathyroid hormone, a stimulator of
resorption, increases the bioactivity of these factors in the
conditioned medium of these cultures.  These results are
significant because IL-1 is among the most potent polypeptide
stimulators of in vitro bone cell activity.  Hence, its production
by bone cultures suggests that it may be a powerful local regulator
of bone cell function.

TNF alpha is another factor that has potent effects on bone cell
function.  In addition, it is frequently produced by the same cells
that produce IL-1 and the effects of IL-1 and TNF on bone are
similar.  Hence, the finding that IL-1 like factors are produced
in bone suggests that TNF like factors are also.

I propose to further examine the mechanisms that regulate the
synthesis and release of IL-1 in bone, identify the cells that
produce it and determine what role it plays in the responses of
bone to other factors.  In addition, I wish to examine whether TNF
is also spontaneously produced by bone cultures.  If it is, I will
perform similar studies to determine its role in bone cell
function.

## Key facts

- **NIH application ID:** 3156019
- **Project number:** 5R01AR031263-10
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **SAM.gov UEI:** H6D6JMXJXDE6
- **Principal Investigator:** Joseph A Lorenzo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $114,173
- **Award type:** 5
- **Project period:** 1982-09-30 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156019

## Citation

> US National Institutes of Health, RePORTER application 3156019, CYTOKINES IN BONE (5R01AR031263-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156019. Licensed CC0.

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