Inhibition of osteoclastogenesis

Details Inhibition of osteoclastogenesis Inhibition of osteoclastogenesis

1999-09-10

2001-05-29

Criares, Theodore J. (Department: 1617)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S415000, C514S573000

Reexamination Certificate

active

06239157

ABSTRACT:

The present invention relates to inhibiting osteoclast production and more particularly to a process and composition for regulating the differentiation of human hematopoietic stem cells into osteoclasts. The invention further relates to reducing bone resorption.
BACKGROUND OF THE INVENTION
Osteoclasts arise from hematopoietic stem cells and are the primary cells responsible for physiological and pathological bone resorption. Changes in the levels of cytokines and growth factors in bone microenvironment cause abnormal bone resorption by the osteoclasts (for a review see Mundy, et al., 1997). Accordingly, forced expression of IL-4 (Lewis, et al., 1993), and G-CSF (Takahashi, et al., 1996) in mice induced osteopenia, while mice overexpressing soluble TNF-&agr; receptor (Ammann, et al., 1997) or depleted of the IL-6 gene (Poli, et al., 1994) are protected against bone loss caused by estrogen deficiency. Recent studies have demonstrated that OPGL is an essential and sufficient regulator of osteoclast differentiation, activity and survival (Kong, et al., 1999).
SUMMARY OF THE INVENTION
It has been found that the differentiation of CD34+ cells into osteoclasts is inhibited by treatment of the hematopoietic stem cells with peroxisome proliferator-activated receptor-&ggr; (PPAR-&ggr;) agonists. The CD34+ cells may be hematopoietic stem cells (HSCs).
Accordingly, the present invention provides a method for inhibiting the differentiation of HSCs into osteoclasts by treating the HSCs with PPAR-&ggr; agonists in an amount sufficient to inhibit differentiation into osteoclasts.
In accordance with an embodiment of the present invention, the production of osteoclasts is reduced, in vivo, by administering an amount of a PPAR-&ggr; agonist in an amount that is effective for reducing such production. The present invention also is applicable to reducing such production, in vitro, by the use of such an agonist.
In accordance with yet another object of the present invention, there is provided a process for treating osteoporosis in an animal, in particular a human, by administering an amount of a PPAR-&ggr; agonist effective for such treatment.
In a preferred embodiment the PPAR-&ggr; agonist is the PPAR-&ggr; ligand 15-deoxy-&Dgr;
12,14
-prostaglandin-J2 (15d-PG-J2).
In another embodiment, bone resorption is inhibited by treatment with a PPAR-&ggr; agonist. More particularly, the bone resorption caused by osteoclasts is inhibited by use of such an agonist.


REFERENCES:
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