The Interrelationship Between Sclerostin and the Wnt Signaling Pathway

Year 2024, Volume: 33 Issue: 3, 186 - 197, 30.09.2024

Rabia Şemsi , Aylin Sepici Dinçel

Abstract

Sclerostin is a glycoprotein that is crucial in bone metabolism and skeletal disorders. It is produced from the SOST gene, which is highly conserved among vertebrates. Osteocytes, bone cells that produce sclerostin, use this protein to antagonize osteoblasts’ canonical Wnt signaling pathway. This pathway is essential for bone formation as it promotes osteoblast proliferation, differentiation, and survival. However, when sclerostin inhibits this pathway, it reduces the +production of new bone tissue. Studies on animals have shown that mechanical loading can decrease sclerostin synthesis in osteocytes by reducing SOST gene expression. This means that when bones are subjected to mechanical stress, such as through exercise or weightlifting, the expression of the SOST gene decreases, leading to a reduction in sclerostin production. This reduction, in turn, increases Wnt signaling and bone formation. Conversely, when mechanical loading is eliminated, such as during prolonged periods of inactivity, sclerostin synthesis increases, leading to a decrease in bone formation. Sclerostin's inhibition of bone formation has been linked to several diseases with high bone mass. For example, sclerostin deficiency leads to sclerosteosis, a rare genetic disorder characterized by increased bone density and thickness. Similarly, another rare genetic disorder known as van Buchem disease is caused by a mutation in the SOST gene, which reduces sclerostin production and increases bone density. This review discusses the basics of Wnt signaling and its role in bone metabolism and skeletal disorders. It also evaluates the clinical significance and future implications of Wnt signaling in osteoporosis and osteoarthritis, two common conditions that affect bone health. Understanding the complex mechanisms of sclerostin and Wnt signaling is crucial for developing new treatments for bone-related diseases and improving bone health.

Keywords

Bone, Bone formation, Wnt Signaling, Sclerostin

Sklerostin ve Wnt Sinyal Yolu Arasındaki İlişki

Abstract

Sklerostin, kemik metabolizmasında ve iskelet bozukluklarında önemli rol oynayan bir glikoproteindir. Omurgalılar arasında yüksek oranda korunmuş olan SOST geninden üretilir. Sklerostin üreten kemik hücreleri olan osteositler, bu proteini osteoblastlardaki kanonik Wnt sinyal yolunu antagonize etmek için kullanır. Bu yol, osteoblastların çoğalmasını, farklılaşmasını ve hayatta kalmasını desteklediği için kemik oluşumu için gereklidir. Bununla birlikte, sklerostin bu yolu inhibe ettiğinde, yeni kemik dokusu üretimini azaltır. Hayvanlar üzerinde yapılan çalışmalar, mekanik yüklemenin SOST gen ekspresyonunu azaltarak osteositlerde sklerostin sentezini azaltabileceğini göstermiştir. Bu, kemikler egzersiz veya ağırlık kaldırma gibi mekanik strese maruz kaldığında, SOST geninin ifadesinin azaldığı ve sklerostin üretiminde bir azalmaya yol açtığı anlamına gelir. Bu azalma da Wnt sinyalinin ve kemik oluşumunun artmasını sağlar. Tersine, uzun süreli hareketsizlik dönemlerinde olduğu gibi mekanik yük ortadan kalktığında, sklerostin sentezi artarak kemik oluşumunda azalmaya yol açar. Sklerostinin kemik oluşumunu engellemesi, yüksek kemik kütlesine sahip çeşitli hastalıklarla ilişkilendirilmiştir. Örneğin sklerostin eksikliği, kemik yoğunluğunun ve kalınlığının artmasıyla karakterize nadir bir genetik bozukluk olan sklerosteoza yol açar. Benzer şekilde, van Buchem hastalığı olarak bilinen başka bir nadir genetik bozukluk, SOST genindeki bir mutasyondan kaynaklanır ve bu da sklerostin üretiminde bir azalmaya ve kemik yoğunluğunun artmasına neden olur. Bu derleme, Wnt sinyalizasyonunun temellerini, kemik metabolizması ve iskelet bozukluklarındaki rolünü tartışmaktadır. Ayrıca kemik sağlığını etkileyen iki yaygın durum olan osteoporoz ve osteoartritte Wnt sinyalinin klinik önemini ve gelecekteki etkilerini de değerlendirmektedir. Genel olarak, sklerostin ve Wnt sinyalizasyonunun karmaşık mekanizmalarını anlamak, kemikle ilgili hastalıklar için yeni tedaviler geliştirmek ve kemik sağlığını iyileştirmek için çok önemlidir

Keywords

Kemik, Kemik oluşumu, Wnt sinyali, Sklerostin

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