Abstract
BackgroundThe infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure. Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. To date, however, the expression levels of CGRP in the IPFP of human knee OA patients have not been examined.MethodsIFFP and synovial (SYN) tissues were harvested from 100 individuals with radiographic knee OA (unilateral Kellgren/Lawrence [K/L] grades 2–4) during total knee arthroplasty and subjected to immunohistochemical analysis for CGRP localization. In addition, the messenger RNA (mRNA) expression levels of CGRP and cyclooxygenase-2 (COX-2) in the collected tissues were evaluated and compared using real-time PCR analysis of total RNA extracts. CGRP and COX-2 mRNA expression were also compared among individuals with K/L grades 2–4.ResultsCGRP-positive cells were detected in the capillaries within the IPFP and lining layer of SYN tissue. The expression levels of CGRP in the IPFP were positively correlated with COX-2 and were significantly higher than those in SYN tissue. CGRP expression in tissue from the KL4 group was twofold higher than that from the KL2 group.ConclusionsThe IPFP of knee OA patients produces relatively high levels of CGRP, which may be regulated by COX-2 at the transcriptional level. Further studies are needed to determine if CGRP levels are directly linked to OA pathology.
Highlights
The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure
Among the molecules found in joint tissue is the vasodilatory neuropeptide calcitonin gene-related peptide (CGRP), which binds to the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) [16]
These findings demonstrate that the IPFP is a source of Calcitonin gene-related peptide (CGRP) in the joint tissue of OA patients
Summary
The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure. Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. Evidence suggests that several joint tissues, including synovial (SYN) tissue [1,2,3], joint capsule [4], and menisci [5,6,7], are involved in the development of OA and OA pain. CGRP expression is increased in SYN of knee OA patients, implicating the involvement of this molecule in inflammation, OA development, and OA pain [17,18,19]. CGRP expression in the IPFP has not been investigated in human OA patients
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