Versican contributes to ligament formation of knee joints.

Tomoko Higuchi,Kanda Fanhchaksai,Keiko Ota,Hideto Watanabe,Takafumi Watanabe,Kazuhisa Yokoo,Hiroshi Furukawa,Daisuke Suzuki,Marco Franchi

doi:10.1371/journal.pone.0250366

Abstract

Versican is a large proteoglycan in the extracellular matrix. During embryonic stages, it plays a crucial role in the development of cartilage, heart, and dermis. Previously, we reported that Prx1-Vcan conditional knockout mice, lacking Vcan expression in mesenchymal condensation areas of the limb bud, show the impaired joint formation and delayed cartilage development. Here, we investigated their phenotype in adults and found that they develop swelling of the knee joint. Histologically, their newborn joint exhibited impaired formation of both anterior and posterior cruciate ligaments. Immunostaining revealed a decrease in scleraxis-positive cells in both articular cartilage and ligament of Prx1-Vcan knee joint, spotty patterns of type I collagen, and the presence of type II collagen concomitant with the absence of versican expression. These results suggest that versican expression during the perinatal period is required for cruciate ligaments’ formation and that its depletion affects joint function in later ages.

Highlights

The joint is formed by apoptosis of undifferentiated mesenchymal cells in the cartilage primordium of long bones
When the joint formation occurs through the accumulation and lining up of mesenchymal cells, Vcan expression is restricted to the joint interzone
We have demonstrated that Vcan expression in the joint of the perinatal period is required for normal development of the jointed appendages, especially of the cruciate ligaments

Summary

Introduction

The joint is formed by apoptosis of undifferentiated mesenchymal cells in the cartilage primordium of long bones. The marginal cells retain pre-chondrocytic nature and serve as articular chondrocytes In this process, versican (Vcan) [1], a chondroitin sulfate (CS) proteoglycan of the extracellular matrix (ECM) type, is expressed with dynamic patterns. We generated and analyzed Prx1-Cre/Vcanflox/flox ( Prx1-Vcan) mice, which lack Vcan expression in mesenchymal condensation areas of cartilage primordium. Whereas these mice are viable and fertile, they exhibit delayed chondrocyte differentiation and joint malformation in digits [28]. We investigated abnormalities in their joint and found malformation of cruciate ligaments in newborn mice These results suggest that Vcan expression in the perinatal period is necessary for the normal formation of jointed appendages and that its impairment causes joint laxity later

Experimental procedures

Results

Discussion