The British Journal of Rheumatology, Vol 36, 831-838, Copyright © 1997 by British Society for Rheumatology
SH Ralston
Nitric oxide (NO) is an important signalling molecule in bone which is
produced in response to diverse stimuli such as pro-inflammatory cytokines,
mechanical strain and sex hormones. Recent work suggests that NO exerts
biphasic effects on bone cell activity: high concentrations of NO inhibit
bone resorption by inhibiting osteoclast formation and by inhibiting the
resorptive function of mature osteoclasts, whereas lower NO concentrations
potentiate cytokine- induced bone resorption and may be essential for
normal osteoclast function. Similarly, growth and differentiation of
osteoblasts are inhibited by high concentrations of NO which may partly be
responsible for the inhibitory effects of pro-inflammatory cytokines on
bone formation. In contrast, lower amounts of NO produced by constitutive
nitric oxide synthase (NOS) enzymes may play a role in regulating normal
osteoblast growth and in mediating the effects of oestrogens on bone
formation. Evidence of inducible nitric oxide synthase (iNOS) expression
has been found in the rheumatoid joint and patients with active rheumatoid
arthritis (RA) have raised levels of NO breakdown products in blood and
urine. This indicates that NO may be involved in the pathogenesis of bone
disease and tissue damage associated with inflammatory conditions such as
RA, and raises the possibility that iNOS inhibitors may be of therapeutic
value in this situation. The observation that both oestrogen and mechanical
strain increase NO production by activating constitutive NOS further
suggests that bone loss associated with oestrogen deficiency and
immobilization may be related to production of NO and may hence be amenable
to treatment with pharmacological NO donors.
REVIEWS
The Michael Mason Prize Essay 1997. Nitric oxide and bone: what a gas!
Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill.
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