# ENDOSTEAL BONE VOLUME REGULATION AND OSTEOPOROSIS

> **NIH NIH R01** · LOMA LINDA UNIVERSITY · 1989 · $163,867

## Abstract

Studies on bone volume regulation are essential to our long term
goals, which are to cure and prevent osteoporosis.  Bone volume is
determined by the rates of bone formation and bone resorption and
recent research in several laboratories including ours suggest that
growth factors may act locally to modulate bone formation by
stimulating both osteoblast proliferation and activity.  To this
end we have purified to apparent homogeneity, a bone cell growth
factor termed Skeletal Growth Factor (SGF) from human bone matrix
and our studies on the structure of human SGF revealed sequence
homology with human IGF-II.  We found multiple growth factors
including SGF/IGF-II, IGF-I, TGF-B, PDGF and basic FGF in humans
bone matrix and in human bone cell conditioned medium. Based on
past studies we and others have proposed the concept that local
production of growth factors plays a key role in the regulation of
bone metabolism.  The primary focus of this project will e to
investigate the regulation of synthesis and secretion of SGF/IGF-
II and its binding proteins.  In this regard, we will test 3
relevant hypotheses: 1) That SGF/IGF-II synthesis is regulated at
several different steps, i.e., a modest of 8 control points
(ranging from transcription to binding in ECF byu binding protein)
is presented, each one of which will be studied.  Additionally, we
will purify SGF.IGF-II binding proteins from bone cell conditioned
medium and from human bone matrix and determine the effects of
binding proteins on SGF/IGF-II induced cell proliferation and
matrix x synthesis. 2) That regulatory agents for growth factor
synthesis are different for different growth factors.  Those to be
compare with SGF.IGF-II include IGF-I, TGFB and basic FGF.  We will
also determine if synthesis of SGF/IGF-II and collagen are
coregulated or independently regulated, 3) That SGF and other
growth factored upon secretion by bonecells are partitioned into
two compartments, a)bone matrix (growth  factors in this
compartment could act at a later time following release by
osteoclast) and b) ECF (growth factors in this compartment could
avt acutely to regulate the proliferation and mature cell functions
of osteoblasts),  We will evaluted this hypotesis by testing
various effectors on this partitioning.  The propose studies will
be carries out using in vitro experimental model systems (bone
cells and vone organs in culture), SGF/IGF-II specific antibodies,
an SGF/IGF-II cDNA prove, radiolavelled SGF and validated growth
factors assays.  It is anticipated that theses studies will provide
valuable information of bone formation at the local level.

## Key facts

- **NIH application ID:** 3155957
- **Project number:** 2R01AR031062-07
- **Recipient organization:** LOMA LINDA UNIVERSITY
- **SAM.gov UEI:** SZAKFNU35ZX5
- **Principal Investigator:** DAVID J BAYLINK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $163,867
- **Award type:** 2
- **Project period:** 1981-08-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155957

## Citation

> US National Institutes of Health, RePORTER application 3155957, ENDOSTEAL BONE VOLUME REGULATION AND OSTEOPOROSIS (2R01AR031062-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155957. Licensed CC0.

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