Critical molecular regulators, histomorphometric indices and their correlations in the trabecular bone in primary hip osteoarthritis

Abstract

These findings indicate an altered state of osteoblast differentiation and function in OA driven by several key molecular regulators. In association with this differential gene expression, an altered state of both trabecular bone remodelling and resulting microarchitecture were also observed, further characterising the pathogenesis of primary hip OA.

Subchondral Bone in Osteoarthritis

“…Interestingly, in the controls but not in the OA samples, positive associations were observed between a number of the molecular and histomorphometric parameters, suggesting, firstly, that the measured expression of genes in bone relates to remodeling mechanisms and, secondly, that these bone regulatory processes may be altered in OA. These data were supported by more recent work, again showing strong associations between the expression of genes, such as CTNNB1 and TWIST1 and structural and remodeling indices in control bone but not in OA and the converse with genes such as MMP25 (Kumarasinghe et al, 2010). Gene expression has also been explored in osteoblasts taken from OA subchondral bone.…”

Evidence for the dysregulated expression of TWIST1, TGFβ1 and SMAD3 in differentiating osteoblasts from primary hip osteoarthritis patients

“…In this study, candidate OA disease genes, TGFb1, SMAD3, WNT5B and TWIST1, previously identified in whole bone extracts 8,11 , were examined at the level of the osteoblast, to determine if they influence osteoblast behaviour in terms of gene expression, mineralisation and mineral composition over an extended time-course, and to examine the relationships between these parameters.…”

“…Examination of gene expression in terms of altered mineralisation, as well as interrelationships between genes, was also conducted to reveal potentially key molecular players driving the dysfunctional properties of the OA osteoblast 11,13,37,38 . From this perspective, the association between TNAP mRNA expression and the Ca:P ratio in OA was significantly different to that in CTL irrespective of time.…”

“…These were macroscopically graded as either Grade III or IV, by assessment of the degree of fibrillation and degeneration 11,12 . The CTL cohort comprised five female non-OA neck of femur fracture cases (mean age ¼ 81 AE 6 years) who were free of any medication affecting bone metabolism and of any extenuating bone pathology 13e18 .…”

“…Femoral trabecular bone from hip OA cases displayed altered material properties and composition 10 . Furthermore, correlations have been observed in OA bone between differentially expressed molecules of the WNT and TGFb pathways, as well as correlations between gene expression and altered histomorphometric indices 11 . Together, these studies suggest that at least a component of OA aetiology resides in the bone and is attributable to an altered state of osteoblast differentiation and function, driven by differential expression of critical molecular regulators 11 .…”