Chief Scientist Ge Xianpeng's team eLife published a paper explaining the source and differentiation

Osteoarthritis (OA) is one of the most common types of arthritis, which can affect all synovial joints in the human body, including temporomandibular joints and limb joints. This disease mainly involves the destruction of articular cartilage, causing pain and movement disorders, seriously affecting the quality of life of patients. At present, there is a lack of effective methods to prevent, prevent, or repair joint cartilage damage in clinical practice. One of the fundamental reasons is that the mechanism of joint cartilage formation is not fully understood. Therefore, elucidating the mechanism of joint cartilage formation, especially the source and differentiation mechanism of joint cartilage stem cells, is crucial for understanding the pathogenesis of OA and developing effective therapeutic drugs and methods for the disease. It is also a cutting-edge fundamental scientific issue that urgently needs to be addressed in the field.

On February 15, 2023, the international academic journal eLife published online a research paper titled "NFATc1 marks artistic cartilage promoters and negatively determined genes artistic cartilage differentiation" by Ge Xianpeng's team, the company's chief scientist. This study for the first time found that NFATc1 is expressed in articular cartilage stem cells and combined with techniques such as in vivo tracing of stem cells, Further clarification of the source of early chondrocyte stem cells in joint development was provided in terms of spatial location, and NFATc1 was identified as a key transcription factor regulating the differentiation of joint chondrocytes. For a long time, NFATc1 has been considered a key gene in regulating osteoclast differentiation and function in the musculoskeletal system, and laboratories such as Clifford Tabin from Harvard Medical School have previously reported that NFATc1 promotes chondrocyte differentiation (which is different from the conclusion of this study). Therefore, this discovery has a disruptive effect on previous related cognition and has been selected as the "eLife digest" as a key recommendation. This paper was published through the eLife traditional peer review process.

This study follows the innovative findings of Professor Ge Xianpeng during his postdoctoral research at Harvard Medical School: NFATc1 and NFATc2 inhibit the formation of multiple osteochondromas in stem cells at ligaments and their attachment points through a mutually compensatory mechanism. NFATc1 and NFATc2 dual gene knockout mice can simulate the pathological changes and clinical manifestations of human multiple osteochondromas, and the dosage of NFAT gene deletion can determine the number and size of osteochondromas, And based on this, a new mechanism of osteochondroma pathogenesis was proposed (Ge et al., JCI Insight 2016, Journal Characteristic Paper). On this basis, Ge Xianpeng's research team combined multiple gene editing mouse models, stem cell in vivo tracing, in vitro culture identification, and high-throughput transcriptomics techniques to further study and discover that NFATc1 is expressed in articular cartilage stem cells, and the stem cells expressed in NFATc1 are located on the lateral wing of the joint primordium in the early stage of joint development, further clarifying the spatial position of joint softness.

Figure 1. Formation of articular chondrocytes by NFATc1+stem cells

(Image source: Zhang F, Wang Y, et al., eLife, 2023)

NFATc1 regulates the differentiation of articular chondrocytes

(Image source: Zhang F, Wang Y, et al., eLife, 2023)

In summary, this study identified NFATc1 as an important molecule for labeling articular cartilage stem cells, further clarifying the early source of articular cartilage stem cells. At the same time, it was found that NFATc1 is a key gene determining the differentiation of articular cartilage cells, and regulating a single gene of NFATc1 is sufficient to induce chondrocyte differentiation. These innovative findings are of great significance for understanding the pathogenesis and treatment of osteoarthritis. At the same time, Ge Xianpeng's research team published a research paper in January 2023 in the comprehensive journal Heliyon of Cell Press, reporting the high expression of NFATC1 in human and mouse periosteal stem cells. These series of studies have identified a new type of bone stem cells with NFATC1 as the molecular feature. Further exploration of these stem cells will help to understand the pathogenesis of bone diseases, including OA, and can be used to develop new treatment methods and drugs.

Link to original paper:https://doi.org/10.7554/eLife.81569