Download biomedica product list
Semaphorin 4D destroys cartilage
Sema4D induces cartilage destruction
Semaphorin 4D destroys cartilage: Semaphorin 4D (Sema 4D) has been identified as an inflammatory cytokine that promotes cartilage destruction. This finding was recently published by Murakami T and colleagues. In a mouse model of inflammatory arthritis, the researchers demonstrated that Sema4D was increased in synovial fluid and loss of Sema4D protected against cartilage degeneration. Click here to learn more.
What is cartilage?
Cartilage is a type of strong and flexible tissue that is found throughout the body. It is a connective tissue that exists in our joints, bones, spine, ears and nose. It protects our joints and our bones, absorbing impact, reducing friction and helping our joints to move smoothly.
If cartilage is degraded, movements will cause friction and pain, leading to swelling and stiffness. Cartilage degradation can be caused through direct injury, osteoarthritis, and aging.
Semaphorin 4D destroys cartilage
Murakami T, Takahata Y, Hata K, Ebina K, Hirose K, Ruengsinpinya L, Nakaminami Y, Etani Y, Kobayashi S, Maruyama T, Nakano H, Kaneko T, Toyosawa S, Asahara H, Nishimura R. Sci Signal. 2022 Nov;15(758):eabl5304. doi: 10.1126/scisignal.abl5304. Epub 2022 Nov 1. PMID: 36318619.
Abstract
Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry-based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction. Sema4d-deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that degrade cartilage, such as matrix metalloproteinases (MMPs) and aggrecanases. The activation of Mmp13 and Mmp3 expression in articular chondrocytes by Sema4D did not depend on RhoA, a GTPase that mediates Sema4D-induced cytoskeletal rearrangements. Instead, it required NF-κB signaling and Ras-MEK-Erk1/2 signaling downstream of the receptors Plexin-B2 and c-Met and depended on the transcription factors IκBζ and C/EBPδ. Genetic and pharmacological blockade of these Sema4D signaling pathways inhibited MMP induction in chondrocytes and cartilage destruction in femoral head organ culture. Our results reveal a mechanism by which Sema4D signaling promotes cartilage destruction.
SEMA4D ELISA kit highlights
|
|
|
|
RELATED PUBLICATIONS
Inhibition of Semaphorin 4D/Plexin-B1 signaling inhibits the subchondral bone loss in early-stage osteoarthritis of the temporomandibular joint. Zhang Z, Lu L, Ye T, Yu S, Zhang J, Zhang M, He F, Liu Q, Yang H, Feng J.Arch Oral Biol. 2022 Mar;135:105365. doi: 10.1016/j.archoralbio.2022.105365. Epub 2022 Feb 2. PMID: 35151027.
Abstract
Objective: The aim of this study was to demonstrate the biological function of Semaphorin 4D (Sema4D)/Plexin-B1 in the bone formation features of osteoblasts in early-stage temporomandibular joint (TMJ) osteoarthritis.
Design: Sema4D/Plexin-B1, expressed by osteoclasts/osteoblasts, plays a balancing role in bone formation and resorption. However, previous studies have mainly focused on bone resorption by osteoclasts in early-stage osteoarthritis. This study used our reported experimental unilateral anterior crossbite (UAC) mouse model to explore subchondral bone changes, which were assessed by micro-CT analysis. The changes in osteoblasts were investigated after the inhibition of Sema4D by BMA-12 injection with the detection of bone formation-related markers. A Transwell migration assay was performed to reveal the specific impact of Sema4D on osteoblasts in vitro.
Results: The data demonstrated that subchondral bone loss in early-stage TMJ osteoarthritis was accompanied by the upregulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D levels could inhibit subchondral bone loss and cartilage degeneration in early-stage TMJ osteoarthritis. In vitro, the results revealed that Sema4D could reduce the expression of osteocalcin and alkaline phosphatase and increase the migrating capability of Plexin-B1-positive osteoblasts.
Conclusions: Our results revealed that elevated Sema4D expression in early-stage TMJ osteoarthritis might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in early-stage osteoarthritis represents a promising strategy for new therapeutic approaches to osteoarthritis.