Expression Patterns of Neurotrophins and Neurotrophin Receptors in Articular Chondrocytes and Inflammatory Infiltrates in Knee Joint Arthritis

Abstract

Background: It is likely that neurotrophins (NTs) are of great importance for the articular cartilage and the inflammation process in arthritis. Methods: The immunohistochemical expression of the NTs nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and the associated receptors p75, TrkA and TrkB was examined in the knee joint of arthritic and healthy mice. Results: Immunoreactions for NGF and BDNF were detected in cells and nerve fiber varicosities in the inflammatory infiltrates of the synovial tissue of arthritic joints but not in synovial tissue of controls. p75-immunoreactive nerve fiber-like strands were detected in inflammatory infiltrates. Immunostaining for NGF, BDNF, p75, TrkA and TrkB was noted in articular chondrocytes. There was a statistically significant decrease in reactions for NGF (p < 0.001), TrkA (p = 0.001) and p75 (p < 0.001) in articular chondrocytes in joints exhibiting severe arthritis. Conclusion: The findings show that an NT system develops in inflammatory infiltrates of the synovial tissue. Furthermore, most interestingly, autocrine/paracrine effects appear to exist concerning NTs for the articular chondrocytes. The downregulated expression of NGF and NT receptors in articular chondrocytes in arthritis is a new aspect concerning the involvement of NTs in cartilage.

Nerve growth factor acts with the β2-adrenoceptor to induce spontaneous nociceptive behavior during temporomandibular joint inflammatory hyperalgesia

“…In this report, the endogenous synthesis of prostaglandin did not facilitate the spontaneous nociceptive response elicited by TMJ injection of NGF. The findings of the current study taken together with the findings that NGF acts on primary afferent receptor (Malik-Hall et al, 2005;Summer et al, 2006) and is produced in inflammatory conditions (Woolf et al, 1996;Amann and Schuligoi, 2000;Grimsholm et al, 2008) suggest that under situation of tissue injury, NGF may act directly on the primary afferent fibers in cooperation with the adrenergic system to induce TMJ pain.…”

“…NGF is up-regulated in a wide variety of inflammatory conditions (Woolf et al, 1996;Amann and Schuligoi, 2000;Banik et al, 2005) including arthritis as demonstrated in the synovial fluid of arthritic patients (Halliday et al, 1998;Grimsholm et al, 2008). Its high and low affinity receptors, TrkA and p75, respectively, are expressed in the dorsal root (Wright and Snider, 1995;Karchewski et al, 1999;Rifkin et al, 2000) and in the trigeminal ganglion cells (Shinoda et al, 2003;Yang et al, 2006;Gaspersic et al, 2007).…”

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

“…Furthermore, hG-CSF has recently been shown to attenuate the impact of aging on BM stem cells and recover age-related functional decline by significantly improving their proliferation activity and growth factor production such as nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF). Both of the latter are found in the synovial membrane, expressed in articular chondrocytes, and play a role in knee arthritis [48], thus bypassing age-related limitations and objections in using AAPBSC in cartilage repair. hG-CSF is not only a hematopoietic cytokine with bone marrow stem cell mobilizing properties [49].…”

Immunofluorescent Triple-Staining Technique to Identify Sensory Nerve Endings in Human Thumb Ligaments

“…As such, the role and expression of p75 may be unique to tissue type and tissue needs at different stages of development, reconstruction, and adaptation [Fundin et al, 1997;Garcia-Suarez et al, 2010]. Recently, p75 has been implicated in the neurotrophin upregulation seen in arthritis [Grimsholm et al, 2008;Barthel et al, 2009], and, although its specific role in arthritic disease is yet to be determined, there is evidence of decreased p75 expression by articular chondrocytes corresponding to an increase of neurotrophins in the synovial fluid of inflamed joints [Grimsholm et al, 2008]. On the other hand, a general decrease of neurotrophins has been correlated to the reduction of sensory nerves that occurs in senescence [Ulfhake et al, 2002].…”