Identification of the calcitonin receptor in osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this study, we sought to further investigate the expression of the CTR in naïve human OA articular chondrocytes to gain further confirmation of the existents of the CTR in articular cartilage.</p> <p>Methods</p> <p>Total RNA was purified from primary chondrocytes from articular cartilage biopsies from four OA patients undergoing total knee replacement. High quality cDNA was produced using a dedicated reverse transcription polymerase chain reaction (RT-PCR) protocol. From this a nested PCR assay amplifying the full coding region of the CTR mRNA was completed. Western blotting and immunohistochemistry were used to characterize CTR protein on protein level in chondrocytes.</p> <p>Results</p> <p>The full coding transcript of the CTR isoform 2 was identified in all four individuals. DNA sequencing revealed a number of allelic variants of the gene including two potentially novel polymorphisms: a frame shift mutation, +473del, producing a shorter form of the receptor protein, and a single nucleotide polymorphism in the 3' non coding region of the transcript, +1443 C>T. A 53 kDa protein band, consistent with non-glycosylated CTR isoform 2, was detected in chondrocytes with a similar size to that expressed in osteoclasts. Moreover the CTR was identified in the plasma membrane and the chondrocyte lacuna of both primary chondrocytes and OA cartilage section.</p> <p>Conclusions</p> <p>Human OA articular cartilage chondrocytes do indeed express the CTR, which makes the articular a pharmacological target of salmon calcitonin. In addition, the results support previous findings suggesting that calcitonin has a direct anabolic effect on articular cartilage.</p

Coarse graining ππ scattering

We carry out an analysis of ππ scattering in the I J = 00, 11 and 20 channels in configuration space up to a maximal center-of-mass energy √ s = 1.4 GeV. We separate the interaction into two regions marked by an elementarity radius of the system; namely, a long distance region above which pions can be assumed to interact as elementary particles and a short distance region where many physical effects cannot be disentangled. The long distance interaction is described by chiral dynamics, where a two-pionexchange potential is identified, computed and compared to lattice calculations. The short distance piece corresponds to a coarse grained description exemplified by a superposition of delta-shell potentials sampling the interaction with the minimal wavelength. We show how the so constructed nonperturbative scattering amplitude complies with the proper analytic structure, allowing for an explicit N/D type decomposition in terms of the corresponding Jost functions and fulfilling dispersion relations without subtractions. We also address renormalization issues in coordinate space and investigate the role of crossing when fitting the scattering amplitudes above and below threshold to Roy-equation results. At higher energies, we show how inelasticities can be described by one single complex and energy dependent parameter. A successful description of the data can be achieved with a minimal number of fitting parameters, suggesting that coarse graining is a viable approach to analyze hadronic processes.Work partially supported by Spanish MINEICO and European FEDER funds (grants FIS2014-59386-P, FIS2017-85053-C2-1-P and FPA2015- 64041-C2-1-P), Junta de Andalucía (grant FQM-225) and the Swiss National Science Foundation