ÖZ
Osteoporoz, kemik yoğunluğunda azalma ve artmış kırık yatkınlığı ile karakterize kompleks bir iskelet hastalığıdır. Gelişiminde yaşlanma, hormonal dengesizlikler ve genetik faktörler rol oynasa da, son çalışmalar doğal bağışıklık reseptörlerinin, özellikle patojen tanıma reseptörlerinin (PRR’ler), patofizyolojisinde çok önemli bir rol oynadığını göstermektedir. Toll-benzeri reseptörler (TLR’ler), NOD-benzeri reseptörler (NLR’ler) ve RIG-I-benzeri reseptörler (RLR’ler) gibi PRR’ler, mikrobiyal bileşenleri ve hücresel hasar sinyallerini tespit ederek kemik yenilenmesini bozan enflamatuvar yanıtları tetikler. Örneğin, NLRP3 inflamazomlarının aktivasyonu, interlökin (IL)-1β ve IL-18 gibi pro-enflamatuvar sitokinlerin salınmasına yol açar ve bu da osteoklast aktivitesini teşvik ederek kemik yıkımını hızlandırır. Benzer şekilde, TLR4 sinyallemesi RANKL ifadesini artırarak osteoklastogenezi ve kemik kaybını daha da destekler. Buna karşılık, deneysel çalışmalar, TLR9 veya NLRP3 gibi belirli PRR’lerin inhibe edilmesinin, enflamasyonu azaltarak ve osteoblast fonksiyonunu yenileyerek kemik kütlesini koruyabildiğini göstermektedir. Doğrudan bağışıklık-kemik etkileşimlerinin ötesinde, PRR’ler aynı zamanda bağırsak mikrobiyotası ile iskelet sağlığı arasındaki karşılıklı iletişimi de sağlar ve bu durum onların sistemik etkilerini ortaya koyar. Bu derleme, osteoporozda PRR mekanizmalarına ilişkin güncel bilgileri bir araya getirerek, bunların kemik oluşumu ve yıkımı üzerindeki çift yönlü etkisini vurgulamaktadır. Bu yolların çözülmesi, PRR aracılı enflamasyonu hedef alan yenilikçi tedaviler için potansiyel sunmaktadır. Gelecek araştırmalar, osteoporoz yönetimi alanında ilerleme sağlamak için daha az çalışılmış PRR’leri, epigenetik etkileri ve bağışıklık-kemik hücre iletişimini incelemelidir.
Anahtar Kelimeler:
Osteoporoz, enflamasyon, patojen tanıma reseptörü
Kaynaklar
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