Öz
Uzun süre kemiğin pasif yerleşik hücreleri olarak kabul edilen osteositlerin, günümüzde iskelet yeniden yapılanmasının ve sistemik metabolizmanın temel düzenleyicileri olduğu anlaşılmıştır. Bu derlemede, osteosit sinyallemesine ilişkin güncel bilgilerin sentezlenmesi, mekanotransdüksiyon mekanizmalarının değerlendirilmesi ve gelecekteki araştırmalara yön verecek temel bilgi boşluklarının belirlenmesi amaçlanmıştır. Ocak 2016 ile Aralık 2024 arasında yayımlanan çalışmalar MEDLINE, PubMed, Embase, Cochrane CENTRAL ve Google Scholar veri tabanlarında taranarak anlatısal bir derleme gerçekleştirilmiştir. Aramada “osteosit sinyallemesi”, “kemik homeostazı” ve “mekanotransdüksiyon” anahtar kelimeleri kullanılmıştır. Deneysel, preklinik, translasyonel ve klinik araştırmalar derlemeye dahil edilmiştir. Osteositler; sklerostin, nükleer faktör-κB ligand reseptör aktivatörü, Wingless ile ilişkili entegrasyon bölgesi ligandları ve fibroblast büyüme faktörü 23 dâhil olmak üzere parakrin ve endokrin mediyatörler aracılığıyla kemik oluşumu ve rezorpsiyonunu koordine eder. Osteositlerin geniş laküno-kanaliküler ağı; sıvı kayma gerilimi, iyon kanalları (örneğin, Piezo1) ve hücre iskeletinin yeniden düzenlenmesi yoluyla mekanik uyaranların algılanmasını sağlar. Osteositler ayrıca mineral metabolizmasını, bağışıklık yanıtlarını, enerji homeostazını ve yaşlanmayı da etkiler. Güncel bulgular, osteositlerin heterojenliğini ve bağlama bağlı sinyal özelliklerini ortaya koymakla birlikte, birincil mekanik algılayıcılar, sinyal hiyerarşisi ve hücresel çıktıların uzamsal düzenlenmesine ilişkin tartışmalar devam etmektedir. Osteositler, mekanik ve biyokimyasal uyaranları bütünleştiren merkezi düzenleyiciler olarak iskelet ve sistemik fizyolojiyi yönlendirir. İn vivo modellerin, uzamsal transkriptomik yöntemlerin ve mekanistik çalışmaların geliştirilmesi, osteosit sinyallemesinin daha iyi anlaşılmasını sağlayarak osteoporoz, metabolik kemik hastalıkları ve kronik enflamasyon için umut verici tedavi olanakları sunabilir.
Anahtar Kelimeler:
Osteosit, mekanotransdüksiyon, kemik yeniden yapılanması, sklerostin, RANKL, Wnt yolağı, FGF23
Kaynaklar
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