PMID- 10071914
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190905
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 24
IP  - 3
DP  - 1999 Mar
TI  - Effect of interleukin-6 secreted by engineered human stromal cells on osteoclasts 
      in human bone.
PG  - 217-27
AB  - The effect of elevated human IL-6 (hIL-6) production by human bone marrow (Hu-BM) 
      stromal cells on osteoclasts in human bone was examined. Human bone was implanted 
      into nonobese diabetic mice with severe combined immunodeficiency 
      (Hu-Bone-NOD/SCID mice). Immunohistochemistry of bone implants and mouse spleens 
      (at 20 weeks), showed human CD45+ cells, B cells, and macrophages in both 
      tissues. Thus, Hu-BM cells survive human bone transplantation and infiltrate 
      mouse tissue. Bone implants had 75 +/- 12% (mean +/- SD) human CD45+ cells, and 9 
      +/- 4% mouse hematopoietic cells. A retrovirus vector containing the human IL-6 
      gene was used to transduce Hu-BM stromal cells (IL-6/stromal) and the PA317 cell 
      line (IL-6/PA317). IL-6/ stromal cells (secreting, on average, 17 microg of 
      hIL-6/10(6) cells per 24 h) were injected directly into human bone implants in 
      Hu-Bone-NOD/SCID mice. IL-6/PA317 cells (secreting 16 microg/mL of hIL-6/10(6) 
      cells per 24 h) were injected intraperitoneally into Hu-Bone-NOD/SCID mice. 
      Analyses of sera from both groups of animals showed elevated levels of IL-6. 
      However, only bone implants engrafted with IL-6/stromal cells had a statistically 
      significant increase in osteoclast-lined mineralized trabecular bone surface 
      (BS). Thus, a high concentration of serum hIL-6 in Hu-Bone-NOD/SCID mice alone 
      does not increase osteoclast-lined BS in bone implants. Most importantly, it is 
      the type of human BM cell that secretes the high levels of hIL-6 that is most 
      critical.
FAU - Sandhu, J S
AU  - Sandhu JS
AD  - Department of Surgery, University of Toronto, Samuel Lunenfeld Research 
      Institutet, Mount Sinai Hospital, ON, Canada.
FAU - Gorczynski, R M
AU  - Gorczynski RM
FAU - Waddell, J
AU  - Waddell J
FAU - Nguyen, H
AU  - Nguyen H
FAU - Squires, J
AU  - Squires J
FAU - Waddell, J
AU  - Waddell J
FAU - Boynton, E L
AU  - Boynton EL
FAU - Hozumi, N
AU  - Hozumi N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (Interleukin-6)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/chemistry/*cytology/*metabolism
MH  - Bone Transplantation/immunology
MH  - Femur/*cytology/physiology/transplantation
MH  - Flow Cytometry
MH  - Hematopoiesis/immunology
MH  - Humans
MH  - Immunocompromised Host
MH  - In Situ Hybridization, Fluorescence
MH  - Interleukin-6/analysis/blood/*metabolism
MH  - Leukocyte Common Antigens/analysis
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Osteoclasts/*physiology
MH  - Severe Combined Immunodeficiency
MH  - Stromal Cells/metabolism
MH  - Transduction, Genetic
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
AID - S8756-3282(98)00172-0 [pii]
AID - 10.1016/s8756-3282(98)00172-0 [doi]
PST - ppublish
SO  - Bone. 1999 Mar;24(3):217-27. doi: 10.1016/s8756-3282(98)00172-0.