Adult Rat Bones Maintain Distinct Regionalized Expression of Markers Associated with Their Development

Abstract

The incidence of limb bone fracture and subsequent morbidity and mortality due to excessive bone loss is increasing in the progressively ageing populations of both men and women. In contrast to bone loss in the weight-bearing limb, bone mass in the protective skull vault is maintained. One explanation for this could be anatomically diverse bone matrix characteristics generated by heterogeneous osteoblast populations. We have tested the hypothesis that adult bones demonstrate site-specific characteristics, and report differences at the organ, cell and transcriptome levels. Limb bones contain greater amounts of polysulphated glycosaminoglycan stained with Alcian Blue and have significantly higher osteocyte densities than skull bone. Site-specific patterns persist in cultured adult bone-derived cells both phenotypically (proliferation rate, response to estrogen and cell volumes), and at the level of specific gene expression (collagen triple helix repeat containing 1, reelin and ras-like and estrogen-regulated growth inhibitor). Based on genome-wide mRNA expression and cluster analysis, we demonstrate that bones and cultured adult bone-derived cells segregate according to site of derivation. We also find the differential expression of genes associated with embryological development (Skull: Zic, Dlx, Irx, Twist1 and Cart1; Limb: Hox, Shox2, and Tbx genes) in both adult bones and isolated adult bone-derived cells. Together, these site-specific differences support the view that, analogous to different muscle types (cardiac, smooth and skeletal), skull and limb bones represent separate classes of bone. We assign these differences, not to mode of primary ossification, but to the embryological cell lineage; the basis and implications of this division are discussed.

DLX3 regulates bone mass by targeting genes supporting osteoblast differentiation and mineral homeostasis in vivo

“…This indicates that Dlx3 regulates osteoblast differentiation in intramembranous and endochondral bones via tissue-or stage-specific molecular mechanisms. This hypothesis is further supported Appendicular skeleton and craniofacial bones display differential molecular fingerprints, 26 one notable difference being that in the appendicular skeleton skeletal patterning and osteoblastogenesis are regulated by HOX TFs, 20 whereas most of the craniofacial bones are Hox free. This Hox status would be determinant in osteogenic potential and cellular plasticity.…”

Corticosterone Regulates the Expression of Neuropeptide Y and Reelin in MLO-Y4 Cells

“…Peripheral reelin mRNA is found in various tissues and cells including the adult mammalian blood, liver, eyes, odontoblasts, osteoblasts, and osteocytes (Kobold et al, 2002;Maurin et al, 2004;Pulido et al, 2007;Smalheiser et al, 2000). The physiological significance of reelin in bone cells is unknown, but earlier studies have suggested a site-specific expression in limb and skull bones/cells and a possible link between reelin and abnormal bone remodeling in the otic capsule (Rawlinson et al, 2009;Schrauwen et al, 2009). Notably, in osteoblast-like cells, the expression of reelin can be dramatically downregulated by certain biological materials and BMP-2 (van der Zande et al, 2010).…”

Atrophy of the residual alveolar ridge following tooth loss in an historical population

“…Alterations in frequency, intensity and direction of such forces might lead to an imbalance of the neuromuscular stability (BudtzJörgensen, 1996;Kingsmill, 1999) and thus to an impaired activation of osteoblasts and osteoclasts, probably resulting in a discrepancy of resorption (Atwood, 1962). As recently shown by Rawlinson et al (2009) also differences in gene expression of developmentally and/or functionally distinct skeletal sites play a role in their response to mechanical stimuli. The described differences in gene expression profiles between the skull vault and limb bones were attributed to cell (osteoblast) populations of distinct embryonic lineages.…”

“…If these models also hold true for the alveolar process of the jaw and other regions of the skull remains to be investigated in more detail. Also the influence of other factors such as regionally different gene expression (long bones vs. cranial vault) resulting in site-specific osteoblast behavior, osteoclast activity and matrix composition has been discussed in this context recently (Rawlinson et al, 2009). However, loss of teeth leads invariably to atrophy of the residual alveolar ridge being irreversible, chronic, progressive and cumulative (Atwood, 1971).…”