MSC-Exos increased chondrogenic genes Col2a1 (type II collagen alpha 1) and aggrecan, decreased hondrocyte hypertrophy markers MMP-13 (matrix metalloproteinase-13) and Runx2 (runt-related transcription factor 2) in chondrocytes isolated from OA model mice.
We have shown that a T(869)-->C polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene, which results in a Leu-->Pro substitution at amino acid 10, is associated with bone mineral density in Japanese adolescents and postmenopausal women, with genetic susceptibility to osteoporosis or spinal osteoarthritis, and with the outcome of treatment for osteoporosis with active vitamin D. I here review our recent studies, which have provided insight into the function of TGF-beta1 as well as into the role of genetic factors in the development of osteoporosis and osteoarthritis.
The results indicate that COMP is the disease susceptibility gene and the c.2152C>T mutation in exon 18 could cause early-onset OA phenotypes in this kindred, which is compatible with a previous report that this mutation also causes a mild form of multiple epiphyseal dysplasia (MED).
Variants within TGFB1, IGF1 and IL1RN could have a role in OA susceptibility; however, replication of these findings is required in an independent study.
We review the increasing evidence implicating COL2A1 mutations in individuals presenting with isolated degenerative joint disease, aiming to alert physicians who assess these patients to this possibility.
Our goal was to establish whether single nucleotide polymorphisms (SNPs) of TGF-β1, TGF-βRI, Smad3 and tissue inhibitor of metalloproteinases 3 (TIMP3), and their interactions, are associated with knee OA.
Long-term Prg4 expression under the type II collagen promoter (Col2a1) does not adversely affect skeletal development but protects from developing signs of age-relatedOA.
Mutations in matrilin-3 result in multiple epiphyseal dysplasia, which is characterized by delayed and irregular bone growth and early onset osteoarthritis.
Using the procedure developed for analysis of the COL2A1 gene, mutations were detected in > 20% of patients with chondrodysplasias and up to 2% of patients with early-onset familial OA.
The T303M polymorphism of the MATN3 gene, which was initially described as associated with hand osteoarthritis, may be more closely linked to trapeziometacarpal osteoarthritis than to digital osteoarthritis.
We demonstrated no evidence of linkage between the COL2A1/VDR locus and nonsyndromic DDH (LOD score < -2), suggesting, although variants in these genes could play a role in osteoarthritis in patients with DDH, they do not contribute to nonsyndromic DDH.
To investigate the relationships between two COL2A1 single nucleotide polymorphisms (SNPs; T2088C and G4006A) and osteoarthritis (OA) in Han Chinese women.
We analyzed the COL2A1 gene in a 27-year-old woman and her 47-year-old mother presenting with severe premature osteoarthrosis and X-ray signs compatible with mild spondyloepiphyseal dysplasia.
Despite studies suggesting associations of OA with both COL2A1 and VDR loci, our results suggest that mutations at the COL2A1/VDR locus do not play an important role as a cause of common OA in the population at large.
We have previously shown that the mutations p.R116W and p.C299S, associated with MED and SEMD, respectively, cause retention of matrilin-3 within the endoplasmic reticulum of primary chondrocytes, while the mutation associated with osteoarthritis, p.T298M, does not hinder secretion.