Journal of Osteoporosis and Physical Activity
Open Access

The Regulation of Wnt Signaling in the Bone Formation and Homeostasis

Wei Ding^{* *}Correspondence: Wei Ding, Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan, Email:

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Description

Osteoporosis, a destructive and asymptomatic skeletal disorder of aging, characterized by compromised bone strength may end up in bone fractures in response to minor trauma. Osteoarthritis is additionally a skeletal disorder that affects the aged population, but it provides protection to fragility fracture risk despite the age-related loss of trabeculate bone. Microstructural analyses of the leg bone have provided proof for an adaptive structure in mechanism of bone osteoarthritis that may preserve the mechanical ability of bone. Indeed, it was shown that there's a different cortical and trabeculate bone distribution in the leg bone of osteoarthritis subjects when compared to those of osteoporotic postmenopausal women with femoral fracture.

The cortical and trabeculate thickness was shown to be higher in osteoarthritis subjects even within the presence of low bone density. These structural variations, particularly the crucial role of residual bone mass distribution, that is, cortical versus trabeculate, higher discriminate hip fracture probability than areal Bone Mineral Density (aBMD) by DXA. As extensively mentioned [1], many hierarchical levels of the leg bone structure are altered in fracture cases due to the loss, throughout aging, of safety mechanisms that seem to be partially preserved in osteoarthritis. It's so crucial to characterize the various biomolecular effectors in osteoporosis and osteoarthritis that result in bone mass deterioration, particularly the cause of the loss of adaptational mechanisms within the former, so as to optimize the prevention and treatment of osteoporotic fractures. Many studies analyzing the expression of osteogenic genes in osteoporosis are set to the Wnt pathway.

The Wnt pathway is especially relevant throughout Mesenchymal Somatic Cell (MSC) commitment towards osteoblastogenesis. Once Wnt is active, the expression of the adipogenic transcription factors is confined, so maintains preadipocytes in an undifferentiated state [2]. Since the maintenance of bone integrity needs mesenchymal stem cell commitment towards osteoblastic lineage, defective Wnt signaling within the osteoporotic bone might impair the tissue response to functional/mechanical demand and thus increase the fracture risk. The downstream effector of Wnt activation, the transcriptional regulator β-catenin, plays disparate roles in numerous phases of bone transforming and microdamage repair and may well be the underlying crucial factor determining the various bone mass distribution in osteoarthritis versus osteoporosis. Indeed, it's renowned that the mechanical adaptation of the skeleton is partly regulated by Wnt which this mechanical adaptation seems to be higher preserved in osteoarthritis versus osteoporosis [3].

Comprehensive analysis of many genes’ expression has known variations in Wnt and growth factor-β/bone morphogenetic protein pathways in the bone of individuals with no proof of joint disease (control) compared to individuals undergoing joint replacement surgery for either chronic hip Osteoarthritis (OA) or broken neck of Femur (F). All of those studies were vital for the identification of the biomolecular targets that probably play pathogenic roles in these skeletal disease processes. However, the all-over loss of bone mass in the elder, freelance of the occurrence of OA or F, impairs full understanding of the causative roles of the various gene expression profiles are noticed.

The bone of a group of elderly postmenopausal women with fragility fracture of the femur (F) displays lower gene expression of Wnt signaling inhibitors and osteogenesis-related genes compared to the same group of postmenopausal women with Osteoarthritis (OA) without breaking of bone. The lower expression of DKK1, SFRP2, and SOST noticed within the F cohort along with the raised protein levels of -catenin didn't result in the activation of a Wnt-related osteogenic response. Indeed, the expressions of RUNX2, OSX, and BGP genes, which are targets of the Wnt-catenin signaling pathway, were lower in the femur than in osteoarthritis.

This analysis showed that after the fracture has occurred there's a body's systemic response to help bone healing by activating osteogenesis [4,5]. This expected postfracture response is usually recommended by a modification in sera of miRNAs affirmative an osteogenic response of the bone and in a decrease of Wnt inhibitors in the bone that triggers β-catenin accumulation. However, though Wnt signaling was detectable up till the stabilization step of β-catenin, the ultimate outcome, that is, upregulation of the gene expression of RUNX2 or OPG didn't occur. The impaired osteogenic response to mechanical demand in fragility-related leg bone fracture in the osteoporotic bone may be assigned a minimum of partly, to inefficient transduction of Wnt signaling and a coherent gene expression profile.

References

1. Mäkinen TJ, Alm JJ, Laine H, Svedström E, Aro HT. The incidence of osteopenia and osteoporosis in women with hip osteoarthritis scheduled for cementless total joint replacement. Bone. 2007;40(4):1041-1047.

   [CrossRef] [Google Scholar] [PubMed]

2. Blain H, Chavassieux P, Portero-Muzy N. Cortical and trabecular bone distribution in the femoral neck in osteoporosis and osteoarthritis. Bone. 2008;43(5):862-868.

   [CrossRef] [Google Scholar] [PubMed]

3. Rubinacci A, Tresoldi D, Scalco E. Comparative high-resolution pQCT analysis of femoral neck indicates different bone mass distribution in osteoporosis and osteoarthritis. Osteoporos Int. 2012;23(7):1967-1975.

   [CrossRef] [Google Scholar] [PubMed]

4. Vestergaard P, Rejnmark L, Mosekilde L. Osteoarthritis and risk of fractures. Calcif Tissue Int. 2009;84(4):249-256.

   [CrossRef] [Google Scholar] [PubMed]

5. Yang L, Udall WJM, McCloskey EV, Eastell R. Distribution of bone density and cortical thickness in the proximal femur and their association with hip fracture in postmenopausal women: a quantitative computed tomography study. Osteoporos Int. 2014;25(1):251-263.

   [CrossRef] [Google Scholar] [PubMed]