Nitric oxide and its role in orthopaedic disease

Christopher H Evans, M. Stefanovic-Racic, J. Lancaster

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Nitric oxide (·NO) is synthesized by the enzyme nitric oxide synthase (NOS). There are 2 constitutive forms of NOS (cNOS) and 1 inducible form (iNOS). Cells containing cNOS rapidly and transiently produce small amounts of NO in response to agonists that raise cytosolic levels of free Ca2+, whereas cells expressing inducible iNOS produce large amounts of ·NO for extended periods after a lag of several hours during which time the enzyme is induced. Until recently, the 2 constitutive isoforms of NOS were thought to be confined to endothelial cells (eNOS) and brain (bNOS or nNOS). However, eNOS and bNOS have been identified in an increasing variety of additional cells. Many, if not most, types of cells are capable of expressing iNOS in response to cytokines, endotoxin, and phagocytosis. Regulation of iNOS occurs at transcriptional, translational, and posttranslational levels. Because ·NO is rapidly diffusible and soluble in hydrophobic and aqueous environments, it is well suited to its role as an intercellular messenger with the unique ability to penetrate solid tissue. However, it is rapidly inactivated by hemoglobin. The biochemistry of ·NO is dominated by its rapid reaction with oxygen and transitional metals, notably iron. The former reaction may be protective, as when neutralizing superoxide (·O2), or harmful in forming additional highly damaging radicals such as peroxynitrite. Interaction of ·NO with iron-containing proteins has a number of sequelae, including the activation of guanylate cyclase, inhibition of mitochondrial respiration, and inhibition of cell division. Nitric oxide has been implicated in a number of conditions of orthopaedic interest, including inflammation, arthritis, osteoporosis, sepsis, ligament healing, and aseptic loosening of joint prostheses.

Original languageEnglish (US)
Pages (from-to)275-294
Number of pages20
JournalClinical Orthopaedics and Related Research
Issue number312
StatePublished - 1995
Externally publishedYes

Fingerprint

Orthopedics
Nitric Oxide
Nitric Oxide Synthase
Iron
Endothelial Cells
Joint Prosthesis
Peroxynitrous Acid
Guanylate Cyclase
Nitric Oxide Synthase Type II
Enzymes
Phagocytosis
Ligaments
Endotoxins
Superoxides
Cell Division
Biochemistry
Osteoporosis
Arthritis
Sepsis
Protein Isoforms

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Surgery

Cite this

Evans, C. H., Stefanovic-Racic, M., & Lancaster, J. (1995). Nitric oxide and its role in orthopaedic disease. Clinical Orthopaedics and Related Research, (312), 275-294.

Nitric oxide and its role in orthopaedic disease. / Evans, Christopher H; Stefanovic-Racic, M.; Lancaster, J.

In: Clinical Orthopaedics and Related Research, No. 312, 1995, p. 275-294.

Research output: Contribution to journalArticle

Evans, CH, Stefanovic-Racic, M & Lancaster, J 1995, 'Nitric oxide and its role in orthopaedic disease', Clinical Orthopaedics and Related Research, no. 312, pp. 275-294.
Evans, Christopher H ; Stefanovic-Racic, M. ; Lancaster, J. / Nitric oxide and its role in orthopaedic disease. In: Clinical Orthopaedics and Related Research. 1995 ; No. 312. pp. 275-294.
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