Two patients with rheumatoid arthritis and one with Sjögren syndrome had a severe sensorimotor neuropathy preceding or up to 5 years after the onset of the disease. Electrophysiologic and sural nerve biopsy studies revealed an axonal neuropathy. Myelinated fibers were affected to a greater extent than unmyelinated axons. Peripheral nerve damage was related to occlusion of the vasa nervorum, since vasculitic involvement of epineurial vessels was observed in all patients. Despite the severity of the neuropathy, it may recover, because, compared with axons, Schwann cells are perhaps less vulnerable to ischemia.
Nuclear receptor retinoid-related orphan receptor alpha (RORα1) is a member of ROR-family receptors. It is broadly expressed in various tissues and organs during embryonic development. However, so far, little is known about its function in bone. Here, we have elucidated the expression and function of RORα1 in human MG-63 osteoblast-like cells. Reverse transcriptase-polymerase chain reaction and immunocytochemical analysis revealed that human MG-63 osteoblasts expressed and produced RORα1. Other cell lines, such as THP-1 monocytes expressed also RORα1. RORα1 over-expression increased alkaline phosphatase, osteocalcin, cell mineralization, and collagen type I mRNA and protein expression, while RORα1 RNA silencing inhibited these responses. In addition, RORα1 over-expression suppressed the tumor necrosis factor-alpha (TNFα)-induced production of cyclooxygenase-2, prostaglandin E(2) , and metalloproteinase-9. Examination of the signaling pathways disclosed that RORα1 was able to block TNFα-evoked nuclear factor-kappaB activation. In conclusion, this study demonstrates that RORα1 is involved in human osteoblast metabolism by stimulating osteoblast marker expression and inhibiting inflammatory responses. The results may encourage further exploration of RORα1 as a potential target for the treatment of bone disorders related to inflammation.
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