骨骼生長的奧秘：GPER-1在青春期發育中的角色
骨骼生長的奧秘：GPER-1在青春期發育中的角色
在青春期，荷爾蒙對我們身體的發育起著至關重要的作用，尤其是雌激素對於長骨的生長。研究指出，雌激素能夠增進在青春期初期的長骨生長，而長骨增長過程中，其中一個重要的角色就是生長板中的軟骨細胞，生長板的軟骨細胞不斷增生、分化和最終骨化，使骨的長度逐漸增加，這個過程稱之為軟骨內骨化(endochondral ossification)。
在我們團隊的研究中發現，在骨生長的過程中，除了傳統位在細胞質內的雌激素受器(ERα、ERβ)外，GPER-1 (G-protein-coupled estrogen receptor-1)這個膜上的雌激素受器也扮演著調節骨生長的角色。在正常小鼠的發育過程中，青春期(4至8週齡)的小鼠生長板中GPER-1高度表達，但在趨近性成熟階段(12至16週齡)逐漸下降，顯示GPER-1在青春期調控生長板發育，而成年後則功成身退。
通過將小鼠軟骨細胞中的GPER-1基因剃除實驗，在基因剃除的小鼠生長過程中可以觀察到體長、體重、脛骨長度和股骨長度的減少。更重要的是，基因剃除小鼠的生長板中細胞數量、生長板增生區的厚度明顯減少，顯示缺乏GPER-1會抑制生長板軟骨細胞增生，進而限制青春期中骨骼的生長。雖然骨生長受到許多因素調控，但這項研究指出青春期時雌性所分泌的雌性素或雄性所分泌的雄性素(可轉換成雌性素）皆可透過GPER-1而促進長骨生長板的軟骨細胞增殖，增加骨長度而長高。
【應用與亮點】
這項研究揭示了無論雌雄性GPER-1的訊息在青春期早期皆能促進長骨生長板的軟骨細胞增殖，進而促進長骨的生長，增加腿長，這發現在骨發育的研究中，提供了一個新的機制探討方向。
【研究團隊】
團隊成員：何美泠特聘教授、張瑞根教授、陳崇桓教授、鄒亞璇、莊淑君
代表單位：再生醫學與細胞治療研究中心
團隊簡介：我們的團隊針對軟骨內骨化的發育過程中，雌激素受器GPER-1所扮演的角色進行分析，建立了軟骨細胞特異性的GPER-1基因剃除小鼠，並發現GPER-1可以促進青春期生長板軟骨細胞增生，這可能是影響長骨發育的潛在因子。
研究聯繫Email：homelin@kmu.edu.tw, jkchang@cc.kmu.edu.tw
期刊發表: Front. Cell Dev. Biol.
論文連結: https://doi.org/10.3389/fcell.2021.710664
The Mystery of Skeletal Growth: The Role of GPER-1 in Adolescent Development
The Mystery of Skeletal Growth: The Role of GPER-1 in Adolescent Development
During puberty, hormones play a crucial role in the development, especially estrogen's impact on the long bone elongation. Studies indicate that estrogen enhances long bone growth in the early stages of puberty. Growth plate chondrocytes are the main cells that contribute to long bone elongation. These cartilage cells continuously proliferate, differentiate, and ossification, gradually increasing the length of the long bones. This process is known as endochondral ossification.
In our research, we demonstrated that not only the traditional intracellular estrogen receptors (ERα, ERβ) but also the membrane estrogen receptor GPER-1 (G-protein-coupled estrogen receptor-1) plays a regulatory role in bone growth. In the normal development of mice, GPER-1 was highly expressed in the growth plates of 4- and 8-week-old mice, with a gradual decline through 12 to 16 weeks, indicating that GPER-1 regulates growth plate development during adolescence but becomes less active in adulthood.
Through experiments where the GPER-1 gene was deleted in mouse cartilage cells, we found that mice lacking GPER-1 exhibited reduced body length, weight, and decreased length of the tibia and femur during the growth process. Significantly, the cell count and thickness of the proliferative zone in the growth plates of GPER-1 deficient mice significantly decreased. This suggests that the absence of GPER-1 inhibits the proliferation of growth plate cartilage cells, thereby restricting skeletal growth during adolescence. Although bone growth is regulated by many factors, this study suggests that during puberty, the estrogen secreted by females or the testosterone secreted by males (which can be converted to estrogen) can promote chondrocyte proliferation in the growth plate of long bones through GPER-1, increasing bone length and contributing to height growth.
Application and Highlights:
This research reveals that GPER-1 positively regulates the proliferation of growth plate cartilage cells in early adolescence, thereby promoting the growth of long bones. This provides a new regulatory mechanism for exploration in the study of bone development.
Research Team Members: Mei-Ling Ho, Je-Ken Chang, Chung-Hwan Chen Ya-Shuan Chou, Shu-Chun Chuang
Representative Department: Regenerative Medicine and Cell Therapy Research Center (RCC)
Introduction of Research Team:
Our research team delved into the involvement of the estrogen receptor GPER-1 in endochondral ossification development. Through the creation of mice with a specific deficiency in the GPER-1 gene within chondrocytes, we observed that GPER-1 has the capacity to stimulate the proliferation of growth plate chondrocytes during puberty. This discovery suggests that GPER-1 could be a significant factor influencing the development of long bones.
Contact Email: jkchang@cc.kmu.edu.tw
Publication: Front. Cell Dev. Biol.
Full-Text Article: https://doi.org/10.3389/fcell.2021.710664
