Browsing by Subject "WNT1"

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  • Lehtovirta, S.; Mäkitie, R. E.; Casula, V.; Haapea, M.; Niinimäki, J.; Niinimäki, T.; Peuna, A.; Lammentausta, E.; Mäkitie, O.; Nieminen, M.T. (2019)
    Objective: WNT signaling is of key importance in chondrogenesis and defective WNT signaling may contribute to the pathogenesis of osteoarthritis and other cartilage diseases. Biochemical composition of articular cartilage in patients with aberrant WNT signaling has not been studied. Our objective was to assess the knee articular cartilage in WNT1 mutation-positive individuals using a 3.0T MRI unit to measure cartilage thickness, relaxation times, and texture features. Design: Cohort comprised mutation-positive (N = 13; age 17-76 years) and mutation-negative (N = 13; 16-77 years) subjects from two Finnish families with autosomal dominant WNT1 osteoporosis due to a heterozygous missense mutation c.652T>G (p.C218G) in WNT1. All subjects were imaged with a 3.0T MRI unit and assessed for cartilage thickness, T2 and T1 rho relaxation times, and T2 texture features contrast, dissimilarity and homogeneity of T2 relaxation time maps in six regions of interest (ROIs) in the tibiofemoral cartilage. Results: All three texture features showed opposing trends with age between the groups in the medial tibiofemoral cartilage (P = 0.020-0.085 for the difference of the regression coefficients), the mutation-positive individuals showing signs of cartilage preservation. No significant differences were observed in the lateral tibiofemoral cartilage. Cartilage thickness and means of T2 relaxation time did not differ between groups. Means of T1r relaxation time were significantly different in one ROI but the regression analysis displayed no differences. Conclusions: Our results show less age-related cartilage deterioration in the WNT1 mutation-positive than the mutation-negative subjects. This suggests, that the WNT1 mutation may alter cartilage turnover and even have a potential cartilage-preserving effect. (C) 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
  • Makitie, Riikka E.; Niinimäki, Tuukka; Suo-Palosaari, Maria; Kampe, Anders; Costantini, Alice; Toiviainen-Salo, Sanna; Niinimäki, Jaakko; Mäkitie, Outi (2020)
    Objective:Mutations in the X-chromosomalPLS3-gene, encoding Plastin 3, lead to severe early-onset osteoporosis, suggesting a major role for PLS3 in bone metabolism. However, the consequences of abnormal PLS3 function in bone and other tissues remain incompletely characterized. This study evaluated spinal consequences of aberrant PLS3 function in patients withPLS3mutations. Design:A cross-sectional cohort study with spinal magnetic resonance imaging of 15PLS3mutation-positive (age range 9-77 years) and 13 mutation-negative (9-70 years) subjects. Images were reviewed for spinal alignment, vertebral heights and morphology, intervertebral disc changes and possible endplate deterioration. Results:Vertebral changes were significantly more prevalent in the mutation-positive subjects compared with the mutation-negative subjects; they were most abundant in upper thoracic spine, and in all age groups and both sexes, although more prominent in males. Difference in anterior vertebral height reduction was most significant in T5 and T6 (p= 0.046 andp= 0.041, respectively). Mid-vertebral height reduction was most significant in T3 and T5 (p= 0.037 andp= 0.005, respectively), and, for male mutation-positive subjects only, in T4 and T6-10 (p= 0.005-0.030 for each vertebra). Most of the abnormal vertebrae were biconcave in shape but thoracic kyphosis or lumbar lordosis were unchanged. Vertebral endplates were well-preserved in the mutation-positive subjects with even fewer Schmorl nodes than the mutation-negative subjects (10 vs. 16). Conclusions:Compromised PLS3 function introduces severe and progressive changes to spinal structures that are present already in childhood, in both sexes and most abundant in upper thoracic spine. Cartilaginous structures are well-preserved.
  • Makitie, Riikka E.; Kampe, Anders J.; Taylan, Fulya; Makitie, Outi (2017)
    Purpose of Review This review summarizes our current knowledge on primary osteoporosis in children with focus on recent genetic findings. Recent Findings Advances in genetic research, particularly next-generation sequencing, have found several genetic loci that associate with monogenic forms of inherited osteoporosis, widening the scope of primary osteoporosis beyond classical osteogenesis imperfecta. New forms of primary osteoporosis, such as those related to WNT1, PLS3, and XYLT2, have identified defects outside the extracellular matrix components and collagen-related pathways, in intracellular cascades directly affecting bone cell function. Summary Primary osteoporosis can lead to severe skeletal morbidity, including abnormal longitudinal growth, compromised bone mass gain, and noticeable fracture tendency beginning at childhood. Early diagnosis and timely care are warranted to ensure the best achievable bone health. Future research will most likely broaden the spectrum of primary osteoporosis, hopefully provide more insight into the genetics governing bone health, and offer new targets for treatment.