Bone
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Comparative Study
A phenotypically restricted set of primary afferent nerve fibers innervate the bone versus skin: therapeutic opportunity for treating skeletal pain.
Although musculoskeletal pain is one of the most common causes of chronic pain and physical disability in both developing and developed countries, relatively little is known about the nerve fibers and mechanisms that drive skeletal pain. Small diameter sensory nerve fibers, most of which are C-fiber nociceptors, can be separated into two broad populations: the peptide-rich and peptide-poor nerve fibers. Peptide-rich nerve fibers express substance P (SP) and calcitonin gene-related peptide (CGRP). ⋯ Whereas the skin is richly innervated by CGRP(+), SP(+), P(2)X(3)(+) and Mrgprd(+) sensory nerve fibers, the bone marrow, mineralized bone and periosteum receive a significant innervation by SP(+) and CGRP(+), but not Mrgprd(+) and P(2)X(3)(+) nerve fibers. This lack of redundancy in the populations of C-fibers that innervate the bone may present a unique therapeutic opportunity for targeting skeletal pain as the peptide-rich and peptide-poor sensory nerve fibers generally express a different repertoire of receptors and channels to detect noxious stimuli. Thus, therapies that target the specific types of C-nerve fibers that innervate the bone may be uniquely effective in attenuating skeletal pain as compared to skin pain.
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During childhood and adolescence, bone mass and lean body mass (LBM) increase till a plateau is reached. In this longitudinal and cross-sectional study, the age of reaching the plateau was evaluated for lumbar spine and total body bone mass measurements and lean body mass. The association between fractures and bone mineral density (BMD) was studied. ⋯ Peak BMD and peak LBM were attained between 18 and 20 years in females and between 18 and 23 years in males in this study using longitudinal and cross sectional data in the age range of 4 to 30 years. A significantly lower total body BMD was seen in participants who had had a fracture and a lower lumbar spine BMD and BMAD in females who had had a fracture. Lumbar spine BMAD Z-score seems to be a good predictor for future fractures.
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Pulsed electromagnetic fields (PEMF) have been proved effective in the prevention of osteoporosis both experimentally and clinically. Chronotherapy studies have shown that circadian rhythm (CR) played an important role in the occurrence, development and treatment of several diseases. CR has also been recognized as an essential feature of bone metabolism. ⋯ Furthermore, the bone turnover biomarkers (serum alkaline phosphatase, serum bone Gla protein and urinary deoxypyridinoline) and the dynamic histomorphometric parameters reflecting the trabecular osteoblast and osteoclast activity (bone formation rate with bone volume as referent, osteoclast number, etc.) in the OVX+DPEMF group decreased to a larger extent compared with the OVX+NPEMF group. In conclusion, the results indicated that CR was an important factor determining the preventive effect of PEMF on osteoporosis and PEMF exposure in the daytime presented better stimulus efficacy in rats. The findings might be helpful for the efficacious use of PEMF mediations, evaluation of PEMF action and experimental design in the future studies of biological effect of electromagnetic fields.
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Animal model for heterotopic ossification (HO) induced by Achilles tenotomy in rats has been used in the literature. However, the molecular mechanism remains unclear. Here, we studied bone and cartilage related genes and their possible roles in this model. ⋯ The presences of the proteins of HIF-1 alpha, Sox9, Runx2, TGF-betas and BMPs within the HO tissues were confirmed by immunohistochemical staining. Our study indicates that HO induced by Achilles tenotomy is by endochondral bone formation, and HIF-1 alpha activation plays an important role during chondrogenesis in this model. Furthermore, the model provides a new experimental system to study endochondral ossification.