<PAGE>


Note:  Confidential treatment requested.  Exhibit omits information that has
       been filed separately with the Securities and Exchange Commission.       

Research Agreement
Dr. Minako Y. Lee

                               RESEARCH AGREEMENT

         This RESEARCH AGREEMENT is entered into as of the 1st day of September,
1996, by and between OSTEX INTERNATIONAL, INC., a Washington corporation, having
its principal place of business at 2203 Airport Way South,  Suite 400,  Seattle,
Washington  98134  ("Ostex"),  and the  UNIVERSITY  OF  WASHINGTON,  having  its
principal office at Seattle, Washington 98195 (the "University").

                                    RECITALS

         A.  Ostex  has an  ongoing  interest  in  certain  research  technology
(including  inventions,  processes,  formulae  and  the  like,  whether  or  not
patentable,  and property eligible for copyright  protection)  entitled "Role of
O-CSF in Osteoclast  Regulation," as more particularly  described in "Exhibit A"
attached hereto (the "Technology").

         B. The Technology has been assigned by the University to the Washington
Research  Foundation  ("WRF") pursuant to Section 3.3 of that certain Technology
Administration Agreement, dated January 1, 1985, between the University and WRF,
as amended  (the "UW  Agreement").  Pursuant to that certain  Exclusive  License
Agreement between Ostex and WRF, dated October 20, 1989 (the "Exclusive  License
Agreement"),  WRF granted Ostex an exclusive,  worldwide  license to make,  have
made, assign, sublicense,  lease, develop, enhance, modify, produce,  reproduce,
demonstrate,  market,  promote,  sell,  distribute,  use,  exploit and otherwise
commercialize and prepare derivations of the Technology.

         C. Ostex and the  University  entered into a Research  Agreement  dated
November  1,  1992,  pursuant  to which  Ostex  funded  the first two years of a
research  program to be conducted by the  University  relating to the Technology
(the "Research Program").

     D. It is in the  mutual  interest  of  Ostex  and the  University  that the
Research Program be continued pursuant to this Agreement.

         E. Ostex is willing to fund  the XXXXXXXXXXX of the Research Program at
and  through  the  University  of  Washington,   Department  of  Biological
Structure, and the University desires to obtain such funding, all subject to and
in accordance with the terms and conditions set forth in this Agreement.

<PAGE>

                                   AGREEMENTS

         In consideration of the covenants and promises contained herein and for
other good and valuable consideration,  the receipt and sufficiency of which are
hereby acknowledged, the parties hereto agree as follows:

         1.       SCOPE AND SCHEDULE

         The Research Program shall be conducted in accordance with the research
proposal  attached  hereto  as  "Exhibit  A" and  incorporated  herein  by  this
reference (the "Research  Proposal"),  and in accordance with mutually agreeable
written modifications  thereof. The Research Program shall be carried out during
the Program Period (as defined below),  unless sooner  terminated or extended as
herein provided.

         2.       PROGRAM PERIOD

         The Program Period initially will be XXXX in duration; commencing XXXX
and  expiring  XXXX,  provided,  however,  that the  parties  may by mutual
agreement  reached no less than  thirty (30) days prior to  expiration  XXXXXXX,
extend the Program Period  forXXXXXXXXXXXXXXXXXXXXXX to commence XXXX and expire
XXXX.

         3.       OSTEX'S PRINCIPAL OBLIGATIONS

                  3.1 During  XXXXXXXXX of the Program  Period,  Ostex shall pay
the University the sum of XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX to cover
all direct  and  indirect  costs of the  corresponding  portion of the  Research
Program, as set forth in the budget section of the Research Proposal.

                  3.2 In the event that the Program  Period is  extended  beyond
XXXXXXX in accordance  with Section 2 above,  Ostex shall during XXXXXXX pay the
University the sum of XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX to cover all
direct and indirect costs of the corresponding  portion of the Research Program,
as set forth in the budget section of the Research Proposal.

         4.       PAYMENT TERMS

                  4.1 During XXXXXXX of the Program  Period,  Ostex shall,  upon
receipt of invoices from the University, pay the University the amount specified
in Section 3.1 above, in accordance with the following schedule:

               PAYMENT DATE                         PAYMENT AMOUNT

         -XXXXXXXXXXXXXXXXXXXXXXXXXXXX                  XXX
           XXXXXXXXXX

         - XXXXXXXXXXXXXXXXXXXXXXXXXXX                  XXX 
         - XXXXXXXXXXXXXXXXXXXXXXXXXXX                  XXX
         - XXXXXXXXXXXXXXXXXXXXXXXXXXX                  XXX

<PAGE>

                  4.2 In the event that the Program  Period is  extended  beyond
XXXXXXX,  Ostex shall,  upon receipt of invoices  from the  University,  pay the
University  during  XXXXXXX  the  amount  set forth in  Section  3.2  above,  in
accordance with the following schedule:

               PAYMENT DATE                         PAYMENT AMOUNT

         - XXXXXXXXXXXXXXXXXXXXXXXXX                   XXX
         - XXXXXXXXXXXXXXXXXXXXXXXXX                   XXX
         - XXXXXXXXXXXXXXXXXXXXXXXXX                   XXX
         - XXXXXXXXXXXXXXXXXXXXXXXXX                   XXX 

                  4.3 The  University  shall submit its  customary  statement of
expenses  incurred under this Agreement within thirty (30) days after the end of
each six-month interval of the Program Period.

         5.       PRINCIPAL INVESTIGATOR

         For purposes of this Agreement,  and pursuant to University policy, Dr.
Minako Y. Lee is designated the principal  investigator of the Research  Program
("Principal Investigator").  The Principal Investigator shall be responsible for
the  direction  and content of the Research  Program,  including  budgeting  and
budget revisions necessary to accomplish the objectives of the Research Program.
Should  the  Principal  Investigator  leave  the  employ  of the  University  or
otherwise   become   unavailable   to  fulfill  her   obligations  as  Principal
Investigator   during  the  Program  Period,   the  University  may  nominate  a
replacement for the position of Principal  Investigator.  If such replacement is
not  acceptable  to Ostex,  the  Research  Program and budget  contained  in the
Research Proposal may be modified to reflect a reduced scope of work, or, at the
option  of Ostex,  may be  terminated  upon  sixty  (60)  days'  notice,  unless
arrangements  acceptable to Ostex can be made to  subcontract  with the departed
Principal  Investigator,  or the  institution at which she is then employed,  to
continue the work described in the Research Proposal.

         6.       CONFIDENTIALITY

         Neither  party  shall  furnish  to  the  other  any   confidential   or
proprietary  information of any third party in connection  with this  Agreement.
Any such information which one party wishes to furnish to the other shall be the
subject of a separate confidentiality agreement between the parties.

         7.       DATA REPORTS AND FACILITIES

                  7.1 The  University  shall,  in  accordance  with  established
University practice,  keep complete,  accurate,  and authentic accounts,  notes,

<PAGE>

data, and records of the work  performed  under this Agreement and shall provide
Ostex with reports  within thirty (30) days  following the end of each six-month
interval of the Program Period. The University shall furthermore submit to Ostex
a  written  and  comprehensive  final  report  within  ninety  (90)  days  after
termination of the Research Program.

                  7.2  At  the  discretion  and  convenience  of  the  Principal
Investigator during the course of the Research Program,  Ostex's representatives
and others  designated by Ostex may be present as observers while various tests,
inspections  and other  aspects of the  Research  Program  are being  conducted.
Ostex's  representatives may consult informally with the Principal  Investigator
regarding the Research Program both personally and by telephone.  The University
acknowledges  and  agrees  that  the  Principal  Investigator  may  serve  as  a
consultant to Ostex during the term of this Agreement.

                  7.3 From its own  resources  and  those  provided  under  this
Agreement,  the University  agrees to make available  laboratory  facilities and
equipment for the Research Program.

         8.       INVENTION RIGHTS

                  8.1 The  University  acknowledges  and  agrees  that:  (i) all
Technology made,  developed or conceived on or before the date of this Agreement
has been  assigned to WRF  pursuant to Section 3.3 of the UW  Agreement,  and no
commitments  have been made with respect to such Technology  pursuant to Section
3.2 of the UW Agreement;  (ii) all Technology made, developed or conceived after
the date of this  Agreement  will be submitted to WRF pursuant to Section 3.1 of
the UW Agreement;  (iii) no  commitment  will be made pursuant to Section 3.1 of
the UW Agreement with respect to Technology  made,  developed or conceived after
the date of this  Agreement  unless Ostex agrees to such  commitment in writing;
and (iv) the  University  shall not  terminate,  amend,  waive or enforce the UW
Agreement,  or any rights or  obligations  thereunder,  in any manner that could
adversely  affect  Ostex's  rights under this  Agreement  unless Ostex agrees in
writing to such termination, amendment, waiver or enforcement.

                  8.2 The University  shall have no right,  title or interest in
any Technology made, developed or conceived by employees or consultants of Ostex
entirely without the use of University facilities.

         9.       PUBLICATION

         The University  will not be restricted  hereunder  from  publishing the
results of research conducted under this Agreement within a reasonable period of
time following  their  availability.  The University  will provide a copy of all
manuscripts to Ostex prior to their  presentation or submission for publication.
In order to  protect  fully the  rights  of the  University  and of  Ostex,  any
contemplated  publication  or  other  dissemination  containing  details  of  an
invention,   whether  or  not  patentable,  will  be  withheld  until  a  patent

<PAGE>

application is filed or other appropriate steps to protect commercial value have
been completed.  Such withholding shall be kept to a minimum and will not exceed
six (6) months, except by mutual agreement between Ostex and the University.

         10.      INDEMNIFICATION

         The  University  and Ostex each agree to  indemnify  and hold the other
party  harmless  from  damage to persons or property  resulting  from any act or
omission on the part of itself, its employees, its agents, or its officers.

         11.      NOTICES

         Any  notice  to be given  hereunder  shall be in  writing  and shall be
deemed received by the addressee on the day delivered if delivered by courier on
a  business  day,  or on the fifth  business  day  following  mailing if sent by
first-class,  certified  or  registered  U.S.  mail,  postage  prepaid,  to  the
following address:

if to the University:   Director, Grant and Contract Services
                        3935 University Way, N.E., JM-24
                        Seattle, Washington 98195

if to Ostex:            Ostex International, Inc.
                        2203 Airport Way South, Suite 301
                        Seattle, Washington 98134
                        Attention:  President

         12.      TERMINATION

                  12.1 This Agreement shall terminate upon the expiration of the
Program  Period as  defined  in Section 2 above;  provided,  however,  that this
Agreement  may be  terminated by either party prior to expiration of the Program
Period upon sixty (60) days' prior written notice, if such party determines,  in
its  discretion,  that the Research  Program is no longer  feasible or desirable
academically,  technically,  or  commercially.  Upon receipt or delivery of such
notice of termination,  the University  shall exert its best efforts to limit or
terminate any outstanding  financial  commitments for which Ostex is responsible
hereunder,  and  Ostex  shall  reimburse  the  University,  to  the  extent  not
previously reimbursed, for all costs incurred by the University for the Research
Program,  including,  without  limitation,  all obligations not cancelable.  The
University  shall  furnish,  within  sixty  (60) days of the  effective  date of
termination,  a final report of all costs  incurred  and all funds  received and
shall  reimburse  Ostex for payments  which may have been  advanced in excess of
total costs incurred, with no further obligations to Ostex.

                  12.2  Notwithstanding  paragraph 12.1 above, in the event that
either party shall be in default of any of its obligations  under this Agreement

<PAGE>

and shall fail to cure such  default  within  thirty  (30) days after  receiving
written  notice  thereof,  the party not in  default  shall  have the  option of
terminating  this  Agreement  by giving  written  notice of  termination  to the
defaulting party, which shall be effective thirty (30) days after delivery.

                  12.3 Termination of this Agreement shall not affect the rights
and obligations of the parties  accrued prior to termination,  or the rights and
obligations set forth in Section 8 above.

         13.      WARRANTS AND COVENANTS BY UNIVERSITY

                  13.1 The University  hereby warrants that it has the right and
authority  to enter  into  this  Agreement  and that the  representatives  whose
signatures  appear hereunder are duly authorized by the University to enter into
this Agreement on behalf of the University.

                  13.2 The University covenants that it will not knowingly enter
into any agreement with any  industrial or commercial  funding source other than
Ostex if such agreement would be inconsistent with the University's  obligations
hereunder.

         14.      GOVERNING LAW

         This  Agreement  shall be governed by and construed in accordance  with
the laws of the State of Washington.

         15.      ARBITRATION AND JURISDICTION

                  15.1 At the request of either party, any  controversy,  claim,
or dispute  arising out of or relating to any provision of this Agreement  shall
be  settled  by  arbitration  to  be  conducted  in  Seattle,  Washington.  Such
arbitration  shall be  conducted  in  accordance  with the rules  applied by the
American  Arbitration  Association.  Judgment  upon any award  rendered  through
arbitration may be entered into any court of competent jurisdiction.

                 15.2     Ostex and the University agree to submit to 
jurisdiction in Seattle, Washington.

         16.      SUCCESSORS AND ASSIGNS

         This Agreement,  including the indemnification provisions hereof, shall
be binding upon and inure to the benefit of the parties hereto, their respective
successors, assigns, and legal representatives.  Ostex may assign this Agreement
to any successor to all or  substantially  all of its business and assets.  This
Agreement  shall not  otherwise be  assignable by either party without the prior
written consent of the other.

<PAGE>

         17.      NO ORAL MODIFICATION

         No  change,  modification,  extension,  termination  or  waiver of this
Agreement,  or any  provision  herein  contained,  shall be valid unless made in
writing and signed by duly authorized representatives of the parties hereto.

         18.      SURVIVAL

         Sections 8 and 9 of this  Agreement  shall  survive any  expiration  or
other termination of this Agreement.

         19.      USE OF NAMES

         Neither  party will use the name of the other party or its employees in
any  advertisement,  press release or publicity  with respect to the  Technology
without the prior written approval of the other party. The University shall have
the right to acknowledge  Ostex's  support of the research  performed under this
Agreement in scientific publications and other scientific communications.

         EFFECTIVE as of the day and year first set forth above.

UNIVERSITY:                                          OSTEX:

By   /S/ DANALD A. ALLEN                 By  /S/ JOHN M. BRENNEMAN
     Donald W. Allen, Director,          John M. Brenneman, Director of Finance
     Grant and Contract Services

     11/21/96                            10/22/96
     Date of signature                   Date of signature


<PAGE>




EXHIBIT A

Continuation of Research proposal:

Role of O-CSF in Osteoclast Regulation

For XXXXXXXXXXXXXXXXXXXXXXXXXXX

Submitted to:

OSTEX International Inc.
2203 Airport Way, S., Suite 301
Seattle, WA.  98l34
Tel: (206) 292-8082
Fax: (206) 292-8625

Principal Investigator:

Minako Y. Lee, ,M.D.
Research Associate Professor
Department of Biological Structure
SM-20

University of Washington
Seattle, WA.  98195
Tel: (206) 685-1514
Fax:(206) 543-1524

1

Lee, Minako Y.

<PAGE>

Budget Request for XXXX X XXXXXXXXXXXXXXXXXX

DETAILED BUDGET FOR THE FIRST 12 MONTHS


Personnel:

Name              Role              %        Salary   Fringe  Total
M. Y. Lee         P.I              40%        XXX      XXX    XXX
Y Igarashi        Senior Fellow    30%        XXX      XXX    XXX
L. Ferguson       Res Tech I       100%       XXX      XXX    XXX
Q. Dang           Hourly                      XXX      XXX    XXX

Subtotal personnel:                                           XXX

Equipments:

Microcentrifuge XXXX, Tissue homogenizer XXXX                 XXX

Supplies:

XXXXXXXXXXXXXXX                                               XXX
XXXXXXXXXXXXXXX                                               XXX
XXXXXXXXXXXXXXX                                               XXX
XXXXXXXXXXXXXXX                                               XXX
XXXXXXXXXXXXXXX                                               XXX
Others XXXX, equipment repair, service: XXX
publication: XXX, photocopies, postage: XXXX                  XXX
XXXXXXXXXXXXXXX                                               XXX
Housing in XXXXXXXXXXXXXXX                                    XXX
Subtotal for supplies:                                        XXX

Total direct costs:        XXX           xxxxxx   Indirect Costs:   xxxxxx

                        xxxxxx          xxxxxx    Indirect Costs:   xxxxxx

Total direct costs for the next XXXX period  xxxxxx  Indirect Costs:  xxxxxx

Total direct and indirect for next XXXX period:  XXXX

<PAGE>



                     xxxxxx   xxxxxx

Personnel
         Salaries    xxxxxx   xxxxxx
         Fringe      xxxxxx   xxxxxx
         Total       xxxxxx   xxxxxx

Equipment            xxxxxx   xxxxxx

Supplies          xxxxxx   xxxxxx

Total             xxxxxx   xxxxxx

BUDGET JUSTIFICATION:

     We are  requesting  salaries  for  personnel  who  will be  working  on the
proposed project at a % effort as indicated.  Dr. Lee will spend xxx of her time
as P.I. A proposed  salary is  commensurate  with her  experience  and  academic
level.  Dr.  Igarashi,  Ph.D.  in  biochemisty,  is an  associate  professor  in
Biochemistry  at Dokkyo  University  School of Medicine,  Japan.  He came to our
laboratory in April 95 as a visiting  scholar to work for 2 years.  He is a well
experienced  biochemist in protein  purification and molecular biology,  and his
contribution  is  very  helpful  to  our  program.  He  will  work  with  us  on
XXXXXXXXXXXX. He needs 30% of his salary support in next year. Ms. Ferguson will
provide  technical  assistance in XXXXX involved in the proposal.  Mr. Dang will
XXXXXXX.

Fringe benefit is calculated at 22% for PI, 25% for the fellow, and 30% for the
research technologist, according to the institutional regulation.  Annual 
inflation rate is calculated at 4%.

Indirect cost rate is as per current agreement between  University of Washington
and OSTEX International Inc.


<PAGE>


Research Proposal:  Role of O-CSF in Osteoclast Regulation

A) SPECIFIC AIMS

One half page redacted
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

B) BACKGROUND AND SIGNIFICANCE:

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
responsible  for  bone   resorption.   It  is  now  well  established  that
Ostoeclasts  are  derived  from  a   hematopoietic   stem  cell  population  and
multinucleated  functional  osteoclasts  are formed by the fusion of mononuclear
precursor  cells  (1,2).  Although it has been  clearly  shown that  osteotropic
hormones such as 1,25  dihydroxyvitamin  D3 (vitamin D3) or parathyroid  hormone
(PTH) play  important  roles in the process of functional  osteoclast  formation
(3), mechanisms of immature  osteoclast  development in the bone marrow is still
poorly understood. Nonetheless, recent studies have gradually revealed that more
and  more  complex  mechanisms  are  involved  in  differentiation  of  immature
osteoclasts from the heterogenous hematopoietic cell population.  Involvement of
not only various interleukins, colony stimulating factors (CSF), growth factors,
and/or  hormones but also soluble  receptors of cytokines (4) and marrow stromal
cell elements have been  suggested to play roles at various stages of osteoclast
development (3).XXXXXXXXXXXXXXXXXXXXXXXXXXX

The remaining page unsder background and significance is redacted
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX


<PAGE>

C) PROGRESS REPORT/ PRELIMINARY STUDIES

Following studies have been conducted in collaboration with laboratories of 
Dr. David Eyre, Department of Orthopedics, Dr. William Osborne, Department of 
Pediatrics, both at the University of Washington, and Dr. Stephen Apone, Ostex
International. Inc.

Two pages redacted
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

PRELIMINARY STUDIES

Two and one half pages redacted
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

<PAGE>




Publications:

M.Y.Lee, P.E.Woods, J.L.Lottsfeldt, N.Ramesh, W.R.A.Osborne, D.R.Eyre: Isolation
and molecular  characterization of a murine osteoclast colony stimulating factor
(O-CSF). J Bone Mineral Research 8: S144, 1993.

T.H.Lee,  K.L.Fevold,  Y.Muguruma,  J.L.Lottsfeldt,  M.Y.Lee.  Relative roles of
osteoclast colony-stimulating factor and macrophage colony stimulating factor in
the course of osteoclast development. Exp Hematol 22:66-73, 1994.

Stephen Apone, Karen Fevold, Minako Lee, David Eyre: A rapid method for  
quantifying osteoclast activity in vitro.  J Bone Mineral Research 9:S178, 1994.

Y.Hayase,  M.Y.Lee:  Osteoclast progenitors develop from primitive hematopoietic
stem cells. Exp Hematol 22:(8), 755, 1994.

Y.Mugururna,   M.Y.Lee:   Osteoclast   progenitors   express  c-Kit,  but  their
differentiation  appears independent of stem cell factor.  Abstract submitted to
the annual meeting for the American Society of Hematology, 1995.

L.E.Purton,  M.Y.Lee,B.Torok-Storb.  Normal human peripheral  blood  mononuclear
cells mobilized with granulocyte  colony-stimulating  factor contain  osteoclast
progenitors.  Abstract  submitted to the annual meeting for the American Society
of Hematology, 1995.

<PAGE>



D) Research plan:

Four pages redacted
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 


<PAGE>

WORK SCHEDULE:
Aim 1 XXXXXXXXXXXXXXXXXXXX
Aim 2 XXXXXXXXXXXXXXXXXXXX
Aim 3 XXXXXXXXXXXXXXXXXXXX


References:

1.  SudaT.  et al., Modulation of osteoclast differentiation.  Endocrine 
Reviews. 13:66-80,1992
2.  Nijweide,PJ.  and GroothR. Ontogeny of the osteoclast. In Biology and 
Physiology of the Osteoclast.  Rifkin, BR and Gay CV eds. p82-97.  CRC press, 
Boca Raton, Florida 1992
3.  Chambers,TJ. Regulation of osteoclast development and function. ibd.
p 106-128.
4.  Tamura, T. et al., Soluble interleukin-6 receptor triggers osteoclast 
formation  by interleukin 6.  Proc. Natl Acad. Sci. 90:11924-1928, 1993
5. Lee, MY., Eyre,  DR.,  Osborne,  WRA.  Isolation of a murine  osteoclast
colony stimulating factor. Proc. Natl. Acad. Sci. 88:8500-8504,1991 
6. Lee, MY.,
Lottsfeldt,  JL. Fevold, KL.  Identification and  characterization of osteoclast
progenitors by clonal analysis of hematopoietic cells. Blood 80:1710-1716,  1992
7.  Metcalf,D.   Hematopoietic   regulators.   Redundancy  or  Subtlety?   Blood
82:35l5-3523, 1993
8.  Kaushansky,   K.,  Lin,N.  and  Adamson,J:   Interleukin  1  stimulates
fibroblasts  to  synthesize   granulocyte-macrophage   and  granulocyte   colony
stimulating factors.  Mechanisms for the hematopoietic response to inflammation.
J Clin Invest 81: 92-97,  1988 
9. Thomson,  B.M.,  Saklatvala,  J. and Chambers,
T.J:  Osteoblasts  mediate  interleukin 1 stimulation of bone  resorption by rat
osteoclasts. J Exp Med 164: 104-112, 1986 
10. Lee,TH., Fevold,KL.,  Muguruma,Y.,
Lottsfeldt,JL.,  Lee,MY. Relative roles of osteoclast  colony-stimulating factor
and   macrophage   colony-stimulating,   factor  in  the  course  of  osteoclast
development. Exp Hematol 22:66-73. 1994 
11. de-la-Mata,J., et al., Interleukin-6
enhances   hypercalcemia   and   bone   resorption   mediated   by   parathyroid
hormone-related protein in vivo. J.Clin Invest. 95:2846-2852, 1995 
12. KodamaH., et al., Congenital  osteoclast deficiency in osteopetrotic 
(op/op) mice is cured by  injections  of  macrophage  colony-stimulating  
factor.  J. Exp.  Med.  173:269-272,  1991 
13. Jilka,R.,  et al.,  Increased  osteoclast  development  after
estrogen  loss:  mediation  by  interleukin-6.   Science  257:88-91,   1992  
14.Horowits,MC.  Cytokines and estrogen in bone: Anti-osteoporotic effects. 
Science 260:626-627,  1993 
15. Rifkin,DB and Moscatelli,  D. Recent  developments in the
cell biology of basic fibroblast  growth factor.  J.Cell Biol 109: 1-6, 1989 
16.Apone,S.,  Fevold,K.,  Lee,M., Eyre,D. A rapid method for quantifying 
osteoclastactivity in vitro.  J Bone Min Res 9:S178,  1994 
17.  Muguruma,Y.  and Lee,  MY.Osteoclast   progenitors  express  c-Kit,  but  
their  differentiation   appears independent of SCF. (submitted) 15

<PAGE>

FOUR EXPRESSION GRAPHS REDACTED ON THIS PAGE