RESUMEN
Osteoblast differentiation is a key process in bone homeostasis. Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis. Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation. However, the bone-related function of plastin 1, another family member of plastins, has not been assessed. In this study, we addressed the functional importance of plastin 1 in osteoblasts. We characterized the expression patterns of plastin 1 during osteoblast differentiation and revealed its important role in this process. In both HEK 293T and hFOB1.19 cells, plastin 1 was demonstrated to regulate intracellular Ca2+. Accordingly, we revealed that higher Ca2+ concentration promotes osteoblast differentiation. Finally, we found that plastin 1 may play a compensatory role in osteoporosis patients with plastin 3 deficiency. Together, our results indicate that plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2+. Our work sheds new light on the role played by plastins in bone homeostasis.
Asunto(s)
Señalización del Calcio , Calcio/metabolismo , Diferenciación Celular , Enfermedades Genéticas Ligadas al Cromosoma X/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Microfilamentos/metabolismo , Osteoblastos/metabolismo , Osteoporosis/metabolismo , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Células HEK293 , Humanos , Masculino , Glicoproteínas de Membrana/genética , Proteínas de Microfilamentos/genética , Osteoblastos/patología , Osteoporosis/genética , Osteoporosis/patologíaRESUMEN
Auditory reception relies on the perception of mechanical stimuli by stereocilia and its conversion to electrochemical signal. Mechanosensory stereocilia are abundant in actin, which provides them with structural conformity necessary for perception of auditory stimuli. Out of three major classes of actin-bundling proteins, plastin 1 encoded by PLS1, is highly expressed in stereocilia and is necessary for their regular maintenance. A missense PLS1 variant associated with autosomal dominant hearing loss (HL) in a small family has recently been reported. Here, we present another PLS1 missense variant, c.805G > A (p.E269K), in a Turkish family with autosomal dominant non-syndromic HL confirming the causative role of PLS1 mutations in HL. We propose that HL due to the p.E269K variant is from the loss of a stable PLS1-ACTB interaction.