Adiponectin inhibits fibrosis of the palmar aponeurosis in Dupuytren’s contracture in male patients

Abstract

AimsDupuytren’s contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis.MethodsWe compared the expression of the adipocytokines adiponectin and leptin in the adipose tissue surrounding the palmar aponeurosis of male patients with Dupuytren’s contracture, and of male patients with carpal tunnel syndrome (CTS) as the control group. We also examined the effects of adiponectin on fibrosis-related genes and proteins expressed by fibroblasts in the palmar aponeurosis of patients with Dupuytren’s contracture.ResultsAdiponectin expression in the adipose tissue surrounding the palmar aponeurosis was significantly lower in patients with Dupuytren’s contracture than in those with CTS. The expression of fibrosis-related genes and proteins, such as types 1 and 3 collagen and α-smooth muscle actin, was suppressed in a concentration-dependent manner by adding AdipoRon, an adiponectin receptor agonist. The expression of fibrosis-related genes and proteins was also suppressed by AdipoRon in the in vitro model of Dupuytren’s contracture created by adding TGF-β to normal fibroblasts collected from patients with CTS.ConclusionFibrosis of the palmar aponeurosis in Dupuytren’s contracture in males may be associated with adiponectin expression in the adipose tissue surrounding the palmar aponeurosis. Although fibroblasts within the palmar aponeurosis are often the focus of attention when elucidating the pathogenesis of Dupuytren’s contracture, adiponectin expression in adipose tissues warrants closer attention in future research.Cite this article: Bone Joint Res 2023;12(8):486–493.

Effects of metformin on knee joint capsule fibrosis in a diabetic mouse model

“… 41 Adiponectin is decreased in the adipose tissue around the palmar aponeurosis of patients with Dupuytren’s contracture, and it suppresses fibrosis of the palmar aponeurosis in a concentration-dependent manner. 20 The current study showed that the addition of adiponectin to db/db mice fibroblasts in vitro suppressed hyperglycaemia-induced upregulation of fibrosis-related genes, excluding TGF-β1, suggesting that adiponectin improves tissue remodelling; in contrast, metformin alone led to an irreversible effect. Thus, metformin-induced inhibition of fibrosis in the knee joint capsule in vivo might be caused by the combinational effect of TGF-β1 inhibition and adiponectin.…”

“…Adiponectin is an important adipokine with anti-inflammatory and antioxidant effects that improves remodelling and suppresses fibrosis in various pathological conditions, such as diabetic nephropathy and atrial fibrillation. 18 - 20 Metformin increases adiponectin secretion. 40 In patients with scleroderma and advanced fibrosis, the abundance of adiponectin and its receptor are reduced, suggesting that adiponectin is involved in progressive fibrosis in chronic fibrotic diseases.…”

“…The concentrations of the high-glucose medium, metformin, and AdipoRon were based on previous reports. 20 , 24 …”

“… 17 The anti-inflammatory and anti-fibrosis effects of adiponectin inhibit tissue fibrosis in the heart, kidney, and ligaments. 18 - 20 However, the effects of metformin on knee joint capsule fibrosis in patients with diabetes remain unclear.…”