RNA interference therapy for autosomal dominant osteopetrosis type 2. Towards the preclinical development
Autosomal Dominant Osteopetrosis type 2 (ADO2) is a rare bone disease characterized by dense and brittle bones due to impairment of osteoclast bone resorption. Dominant negative mutations of the CLCN7 gene affect about 70% of ADO2 patients. ADO2 has no cure and our recent work established that it is suitable for gene silencing by a specific small interfering RNA that does not affect the normal mRNA, thus inducing a condition of pseudo-haplosufficiency and rescuing the bone phenotype. We performed a systematic study to test the likelihood that the therapy could progress towards clinical trials, treating Clcn7G213R/WT ADO2 m...
Source: Bone - February 28, 2018 Category: Orthopaedics Authors: Antonio Maurizi, Mattia Capulli, Rajvi Patel, Annabel Curle, Nadia Rucci, Anna Teti Tags: Full Length Article Source Type: research
Amino acids as signaling molecules modulating bone turnover
Except for the essential amino acids (AAs), much of the focus on adequate dietary protein intake has been on total nitrogen and caloric intake rather than AA composition. Recent data, however, demonstrate that “amino-acid sensing” can occur through either intracellular or extracellular nutrient-sensing mechanisms. In particular, members of the class 3 G-protein coupled receptor family, like the calcium-sensing receptor are known to preferentially bind specific AAs, which then modulate receptor activat ion by calcium ions and thus potentially impact bone turnover. (Source: Bone)
Source: Bone - February 27, 2018 Category: Orthopaedics Authors: Ke-Hong Ding, Michael Cain, Michael Davis, Clare Bergson, Meghan McGee-Lawrence, Crystal Perkins, Trevor Hardigan, Xingming Shi, Qing Zhong, Jianrui Xu, Wendy B. Bollag, William Hill, Mohammed Elsalanty, Monte Hunter, Maria C. Isales, Patricia Lopez, Mark Tags: Review Article Source Type: research
Biochemical transformation of calciprotein particles in uraemia
Calciprotein particles (CPP) have emerged as nanoscale mediators of phosphate-induced toxicity in Chronic Kidney Disease (CKD). Uraemia favors ripening of amorphous CPP (CPP-I) to the crystalline state (CPP-II) but the pathophysiological significance of this transformation is uncertain. Clinical studies suggest an association between CPP ripening and inflammation, vascular dysfunction and mortality. Although ripening has been modelled in vitro, it is unknown whether particles synthesised in serum resemble their in vivo counterparts. (Source: Bone)
Source: Bone - February 27, 2018 Category: Orthopaedics Authors: Edward R. Smith, Tim D. Hewitson, Eric Hanssen, Stephen G. Holt Tags: Full Length Article Source Type: research
A soluble activin type IIA receptor mitigates the loss of femoral neck bone strength and cancellous bone mass in a mouse model of disuse osteopenia
Disuse causes a rapid and substantial bone loss distinct in its pathophysiology from the bone loss associated with cancers, age, and menopause. While inhibitors of the activin-receptor signaling pathway (IASPs) have been shown to prevent ovariectomy- and cancer-induced bone loss, their application in a model of disuse osteopenia remains to be tested. Here, we show that a soluble activin type IIA receptor (ActRIIA-mFc) increases diaphyseal bone strength and cancellous bone mass, and mitigates the loss of femoral neck bone strength in the Botulinum Toxin A (BTX)-model of disuse osteopenia in female C57BL/6J mice. (Source: Bone)
Source: Bone - February 27, 2018 Category: Orthopaedics Authors: Andreas Lodberg, Marco Eijken, Bram C.J. van der Eerden, Mette Wendelboe Okkels, Jesper Skovhus Thomsen, Annemarie Br üel Tags: Full Length Article Source Type: research
