Research

Life Sciences & Biotechnology

Title :	Investigation of joint micro-environment alteration on mechanically sensitive ion channels (Piezo1/2, TRPV4) in articular cartilage homeostasis(J5G5A5-K5A5-O6G5A5-K5A5-N8G5A5-K5A5-N10G5A5-K5A5-M12G5A5-K5A5-M14G5A5-K5A5-M16G5A5-K5A5-M18G5A5-K5A5-M20G5A5-K5A5-M22G5A5-K5A5-M24G5A5-K5A5-M26G5A5-K5A5-L28G5A5-K5A5-L30G5A5-K5A5-L32G5A5-K5A5-K33G5A5-K5A5-L33A5-M33A5-N33A5-O33A5-L33A5-L35A5-M33A5-L33A5-K33A5-L33A5-M33A5-L33A5-K33A5-I33)
Area of research :	Life Sciences & Biotechnology
Principal Investigator :	Dr. Amaresh Kumar Singh, Banaras Hindu University, Uttarpradesh
Timeline Start Year :	2024
Timeline End Year :	2027

Details

Executive Summary :

The articular cartilage is present at weight-bearing joints. Being in such a mechanical environment it is specialized to have high sensitivity to mechanical signals and stimuli from their micro-environment via mechanically sensitive ion channels (MSCs). The synchronous mechanical loading modulates the homeostasis of chondrocytes, however mechanical overload leads to different degrees of damage in articular cartilage. The mechanical loading is sensed by MSCs that translates the mechanical stimuli into biomechanical signal and their dysfunction causes degradation of articular cartilage. Recent findings in our laboratory indicate inflammatory condition in joint due to macrophages polarization from M2-M1, presence of DAMPS due to cartilage damage changes the micro-environment of the joint from normal to inflammatory state. Further, we also noted that ectopic BMP signaling in articular cartilage leads to osteoarthritis-like-phenotype without any surgical intervention and surgical osteoarthritis induction in mice model activates ectopic BMP signaling and inflammatory mediators like Nf-kB, IL1? and TNFalpha in adult articular cartilage. Therefore, we propose a line of investigation of ectopic BMP signaling activation on mechanically sensitive ion channels (especially Piezo 1/2 and TRPV4) and inflammation during the onset and progression of osteoarthritis. Objectives and approaches- 1. Impact of ectopic BMP signaling on mechanically sensitive ion channels (MSCs) and inflammation in chondrocytes- An in-vitro approach 2. Investigation of Piezo1 and TRPV4 dysfunction induced articular cartilage degradation in normal and surgically induced osteoarthritic mice model 3. Evaluation of disease kinetics in absence of local inflammatory partner synovial macrophages and inhibition of MSCs. Impact- Understanding the impact of joint micro-environment alteration on the disease onset and progression may open a new avenue to halt the progression of the disease already set in the patients and help us to develop prevention at the initial stage of osteoarthritis.