Deregulation of bone forming cells in bone diseases and anabolic effects of strontium-containing agents and biomaterials.

Shuang Tan,Xiaomei Zhu,Weihong Yi,Guang-Qian Zhou,Huajie Guo,Ping Ao,Binbin Zhang

doi:10.1155/2014/814057

Abstract

Age-related bone loss and osteoporosis are associated with bone remodeling changes that are featured with decreased trabecular and periosteal bone formation relative to bone resorption. Current anticatabolic therapies focusing on the inhibition of bone resorption may not be sufficient in the prevention or reversal of age-related bone deterioration and there is a big need in promoting osteoblastogenesis and bone formation. Enhanced understanding of the network formed by key signaling pathways and molecules regulating bone forming cells in health and diseases has therefore become highly significant. The successful development of agonist/antagonist of the PTH and Wnt signaling pathways are profits of the understanding of these key pathways. As the core component of an approved antiosteoporosis agent, strontium takes its effect on osteoblasts at multilevel through multiple pathways, representing a good example in revealing and exploring anabolic mechanisms. The recognition of strontium effects on bone has led to its expected application in a variety of biomaterial scaffolds used in tissue engineering strategies aiming at bone repairing and regeneration. While summarizing the recent progress in these respects, this review also proposes the new approaches such as systems biology in order to reveal new insights in the pathology of osteoporosis as well as possible discovery of new therapies.

Highlights

Bone remodeling is a physiological process that maintains the integrity of the skeleton by removing old bone and replacing it with young matrix
In murine mesenchymal stem cells (MSCs) cultures, strontium increased Runx2 expression and matrix mineralization and decreased peroxisome proliferatoractivated receptor gamma 2 (PPARc2) expression and adipogenesis. This effect was associated with enhanced expression of the Wnt noncanonical representative Wnt5a and adipogenic modulator Maf and was abrogated by Wntand nuclear factor of activated T-cells (NFATc) antagonists, indicating a critical role for the Wnt and NFATc/Maf signaling in the switch in adipogenesis to osteoblastogenesis induced by strontium [89]
Aging is associated with impaired bone formation as a principal pathogenetic mechanism mediating bone fragility in osteoporosis

Summary

Introduction

Bone remodeling is a physiological process that maintains the integrity of the skeleton by removing old bone and replacing it with young matrix. In the case of the age-related bone loss or osteoporosis, the osteoblast-mediated bone formation is severely impaired [1, 2] due to decreased number and activity of individual osteoblastic cells. Such dysfunctions of osteoblasts may be caused by extrinsic mechanisms, such as changes in levels of systemic hormones and growth factors of bone tissues, and intrinsic mechanisms such as cellular apoptosis and senescence [2,3,4]. Active and mature osteoblasts synthesizing bone matrix have large nuclei, enlarged Golgi structures, and extensive endoplasmic reticulum These osteoblasts secrete type I collagen and other matrix proteins vectorially toward the bone formation surface. Osteocytes are linked metabolically and electrically through gap junctions composed primarily of connexin 43, which are required for osteocyte maturation, function, and survival [18]

The Molecular Regulation of Osteoblast Differentiation and Function

Deregulation of Bone Forming Cells in Diseases

Anabolic Effects of Strontium-Containing Agents on Osteoblasts

Molecular Basis of the Role of Strontium in Bone Forming Cells

Strontium-Integrated or Substituted Biomaterials for Bone Regeneration

Conclusion and Future Perspectives