Muscone Protects Vertebral End plate Degeneration by Antiinflammatory Property
From: Clin Orthop Relat Res. 2009 Sep 18
Neck pain is one of the most common chronic conditions affecting quality of life and sometimes causing disability in adults. Most chronic neck pain is the result of degeneration of the intervertebral discs in the cervical spine. An intact end plate cartilage is critical for normal disc functions, as the major nutrient supply of the discs is diffused through the end plates. Pathological changes in end plate cartilage are closely related to disc degeneration and thus to cervical spondylopathy. Prevention and reduction of lesions to the vertebral end plate are high research priorities.
IL-1beta may play an important role in intervertebral disc degeneration. This being the case, inhibiting IL-1beta could provide a therapeutic approach for reducing or preventing disc degeneration. Muscone reportedly relieves pain and suppresses inflammation. Therefore, the authors asked whether muscone, a potent antiinflammatory agent, could reduce proinflammatory cytokines in vitro (end-plate cartilage cultures) and end-plate degeneration in vivo (a rat model that induces intervertebral disc degeneration). In vitro, muscone reversed IL-1beta-induced upregulation of IL-1beta, tumor necrosis factor alpha, cyclooxygenase 2, inducible nitric oxide synthase, matrix metalloproteinase 13, aggrecanase 2, and nitric oxide and downregulation of Col2alpha1 and aggrecan. Pretreatment with muscone (6.25, 12.5, 25 mumol/L) inhibited the IL-1beta-induced phosphorylation of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinase in a dose-dependent manner. In vivo, muscone inhibited the expression of prostaglandin E2, 6-keto-prostaglandin F1alpha, IL-1beta, and tumor necrosis factor alpha and recovered the structural distortion of the degenerative disc. The findings suggest muscone is a promising agent for treating intervertebral disc degeneration through its antiinflammatory effects.
