Pre-proenkephalin 1 is Downregulated Under Unloading and is Involved in Osteoblast Biology.

Pre-proenkephalin 1 (Penk1) is a pro-neuropeptide that belongs to the typical opioid peptide's family, having analgesic properties. We previously found Penk1 to be the most downregulated gene in a whole gene profiling analysis performed in osteoblasts subjected to microgravity as a model of mechanical unloading. In this work, Penk1 downregulation was confirmed in the bones of two in vivo models of mechanical unloading: tail-suspended and botulinum toxin A (botox)-injected mice. Consistently, in the sera from healthy volunteers subjected to bed rest, we observed an inverse correlation between PENK1 and bed rest duration. These results prompted us to investigate a role for this factor in bone. Penk1 was highly expressed in mouse bone, but its global deletion failed to impact bone metabolism in vivo. Indeed, Penk1 knock out (Penk1-/-) mice did not show an overt bone phenotype compared to the WT littermates. Conversely, in vitro Penk1 gene expression progressively increased during osteoblast differentiation and its transient silencing in mature osteoblasts by siRNAs upregulated the transcription of the Sost1 gene encoding sclerostin, and decreased Wnt3a and Col1a1 mRNAs, suggesting an altered osteoblast activity due to an impairment of the Wnt pathway. In line with this, osteoblasts treated with the Penk1 encoded peptide, Met-enkephalin, showed an increase of Osx and Col1a1 mRNAs and enhanced nodule mineralization. Interestingly, primary osteoblasts isolated from Penk1-/- mice showed lower metabolic activity, ALP activity, and nodule mineralization, as well as a lower number of CFU-F compared to osteoblasts isolated from WT mice, suggesting that, unlike the transient inhibition, the chronic Penk1 deletion affects both osteoblast differentiation and activity. Taken together, these results highlight a role for Penk1 in the regulation of the response of the bone to mechanical unloading, potentially acting on osteoblast differentiation and activity in a cell-autonomous manner.

Conservación de la diversidad genética en el Perú: desafíos en la implementación del régimen de acceso a recursos genéticos y distribución de beneficios / Conserving the genetic diversity in Peru: challenges in the implementation of an access and benefit-sharing regime

Esta contribución debate los grandes retos que enfrenta Perú en la implementación nacional del régimen de acceso a recursos genéticos y distribución de beneficios, tema conocido por las siglas "ABS" del inglés Access and Benefit-Sharing. El ABS es un mecanismo que incentiva la conservación de la diversidad genética mediante la distribución justa y equitativa de los beneficios que se deriven de la utilización de recursos genéticos entre el país que los provee y el usuario de éstos. Perú afronta cuatro desafíos en relación con el tema: (1) su procedimiento de acceso a recursos genéticos es complejo y burocrático, desalentándose así la negociación de contratos sobre ABS. (2) el rol de la "institución nacional de apoyo" ha sido desvirtuado, exacerbándose su función de mero controlador; con ello se han perdido valiosas colaboraciones científicas a favor de las instituciones científicas locales. (3) la legislación peruana sobre ABS posee efectos retroactivos, infringiendo el principio de seguridad jurídica que debe reinar en toda relación contractual. (4) si bien se han previsto medidas de cumplimiento y un punto de verificación de acuerdo a lo establecido por el Protocolo de Nagoya, no se establece un control sobre la legalidad del acceso a recursos genéticos y conocimiento tradicional asociado al uso de éstos cuando ellos provengan de cualquier otro país que no sea el Perú. Al finalizar el artículo se proponen algunas mejoras a realizar a fin de afrontar los desafíos encontrados en el estudio.

This essay intends to debate the major challenges that Peru faces as it implements a national regime on Access to genetic resources and Benefit-Sharing (ABS). The ABS encourages the conservation of genetic diversity by means of the fair and equitable distribution of the benefits arisen from the utilization of genetic resources. Distribution is to take place between the providing country and the user of the resources. Peru features four main weaknesses in relation to ABS: (1) Firstly; its national legislation on the topic sets a bureaucratic and complex procedure that hinders the negotiation of fructiferous ABS contracts. (2) The role of the "national scientific partner" has been distorted and true opportunities for scientific cooperation are missed. (3) Peruvian legislation on ABS establishes retroactive effects infringing the principle of legal certainty. (4) Even though the national legal framework establishes a set of compliance measures and a checkpoint to verify the legal access of genetic resources in accordance to the Nagoya Protocol, these measures do not cover the control of genetic resources and traditional knowledge associated to their utilization from countries other than Peru. Improvements to face the challenges encountered are offered at the end of the article.