# HC03-SECRETION & CELL VOLUME REGULATION BY OSTEOBLASTS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1989 · $128,920

## Abstract

One of the critical functions of the osteoblast is matrix
mineralization.  To accomplish this task, the osteoblast must be
able to influence the pH and ion current of the fluid in the
demarcation zone.  It is likely that the osteoblasts are capable of
generating and maintaining gradients of HCO3-, Cl-, Na+, K+ and
Ca2+ between the plasma and bone extracellular fluid of the
demarcation zone.  These cells also undergo marked shape
changes during hormonal stimulation.  Maintenance of the ionic
gradients, in particular Ca2+ and HCO3-, are essential for bone
remodeling.  Establishing vectorial transport and transcellular
ionic gradients require polarized localization of ion transport
pathways.  The nature of the ionic pathways and their localization
in the osteoblasts are not known.  It is also not known whether the
shape changes observed in response to calcitropic hormones are
also accompanied by volume changes.  We will use the
osteosarcoma cell line UMR 106, and primary cultures of
osteoblast-like cells from long bone to:  a) identify and then
kinetically characterize the ionic pathways which participate in
cytosolic pH regulation by the osteoblast.  These ionic pathways
include Cl- dependnt HCO3- secretion (Cl-/HCO3-), Na+/H+
exchanger K+ and Cl- conductances nd KCl or 3NaKCl2
cotransporters.  This will be achieved by measurements of pHi and
(Ca2+)i with the pH and Ca2+ sensitive dyes BCECF and Fura 2,
respectively, and net, undirectional and exchange transport of 36
Cl-, 22Na, and 86Rb.; b) localize these ionic pathways to the
membrane facing the BECF or the membrane facing plasma.
UMR-106 and normal rat osteoblast-like cells will be grown on
collagen coated filters and placed in chamber.  The ionic
transporters facing the collagen matrix or the medium will be
identified.  In parallel, the ionic transport characteristics of
vesicles prepared from different portions of the osteoblast plasma
membrane will be studied.  These ionic pathways will be examined
within the framework of cell volume regulation by these cells.
Finally, the effect of hormones such as PTH2+ Vitamin D,
prostoglandins, epidermal growth factor, and second messengers
such as Ca2+, cAMP, and protein Kinase C activation, on these
ionic pathways will be studied as outlined above.

## Key facts

- **NIH application ID:** 3159243
- **Project number:** 5R01AR039245-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** Shmuel Muallem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $128,920
- **Award type:** 5
- **Project period:** 1988-12-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159243

## Citation

> US National Institutes of Health, RePORTER application 3159243, HC03-SECRETION & CELL VOLUME REGULATION BY OSTEOBLASTS (5R01AR039245-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3159243. Licensed CC0.

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