# MECHANISMS OF TGFB ACTIVATION IN BONE MICRO-ENVIRONMENT

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 1988 · $93,676

## Abstract

Transforming growth factor beta (TGF beta) is a polypeptide growth
regulator with bifunctional effects on cell proliferation.  The TGF
beta homodimer (25,000 daltons) has been purified from platelets
and from bone.  We have found that TGF beta may act as a coupling
factor which links osteoblast activity with prior bone resorption,
and thereby plays an important role in bone remodeling.  TGF beta
is released from organ cultures of murine calvaria in an inactive
large molecular weight complex and is activated by decreasing pH,
suggesting the presence of a binding protein attached through
hydrogen bonding.  Our crosslinking studies using I125 TGF beta and
the crosslinking agent disuccinimidyl suberate have revealed by
autoradiography on SDS-PAGE a binding protein (BP) greater than
200,000 daltons.  We have coupled purified BSA-free TGF beta to 6%
cross-linked agarose beads followed by incubation with the BP-TGF
beta complex fraction from a Sephadex G-200 column.  The material
eluted from the TGF beta coupled beads was applied to SDS-PAGE and
the major molecular species was approximately 300,000 MW.  We plan
to examine the mechanism whereby TGF beta is released from its
binding protein and thereby activated.  We have found that bone--
derived. TGF beta is activated by low pH.  Mineral removal is
dependent on acid production, optimal activity of many enzymes is
at acid pH and acid conditions exist under the ruffled border of
the actively resorbing osteoclast.  Enzymes such as plasmin may
also play a role in TGF beta activation as osteoblasts have been
shown to secrete plasminogen activator.  In this proposal we plan
to investigate potential mechanisms of regulation of TGF beta
activity via dissociation of the TGF beta monomer from it binding
protein.  We also plan to use the techniques we have developed in
our preliminary data to purify the binding protein for bone-derived
TGF beta to homogeneity.

## Key facts

- **NIH application ID:** 3159389
- **Project number:** 1R01AR039357-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **SAM.gov UEI:** C3KXNLTAAY98
- **Principal Investigator:** Lynda F Bonewald
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $93,676
- **Award type:** 1
- **Project period:** 1988-09-30 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159389

## Citation

> US National Institutes of Health, RePORTER application 3159389, MECHANISMS OF TGFB ACTIVATION IN BONE MICRO-ENVIRONMENT (1R01AR039357-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159389. Licensed CC0.

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