The alteration of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in the knee joints of osteoarthritis mice

Background: To clarify the expression and distribution of ADAMTS1, ADAMTS2 and ADAMTS5 in knee joints of osteoarthritis (OA) mice. Methods: OA was established via anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6J mice. The morphology change of OA was analyzed by Micro-CT. Histologic analysis was used to evaluate symptomatic change in articular cartilage and subchondral bone. Quantitative real-time PCR (qPCR) was used to analyze mRNA expressions of ADAMTS family in bone-related tissues and cells. Immunofluorescence staining was used to analyze the expressions and distributions of ADAMTS1, ADAMTS2, and ADAMTS5, as well as the condition of inflammation of OA.Results: Cartilage deterioration, significant reduction of collagen and proteoglycan components in the cartilage matrix happened in ACLT-induced OA mice, along with increased inflammatory response and osteoclast activity. Among ADAMTS, the gene expression levels of ADAMTS1, ADAMTS2 and ADAMTS5 were ranked top 5 in cartilage/chondrocytes, osteogenic tissue/osteoblasts and cortical bone/osteocytes. After ACLT surgery, the expressions of ADAMTS1, ADAMTS2 and ADAMTS5 all increased in articular cartilage, growth plate and subchondral bone of knee joints. Conclusion: The enhanced expressions of ADAMTS1, ADAMTS2 and ADAMTS5 after ACLT surgery provide a further understanding in degenerative change of OA.

Developmental and Evolutionary Allometry of the Mammalian Limb Skeleton

The variety of limb skeletal proportions enables a remarkable diversity of behaviors that include powered flight in bats and flipper-propelled swimming in whales using extremes of a range of homologous limb architectures. Even within human limbs, bone lengths span more than an order of magnitude from the short finger and toe bones to the long arm and leg bones. Yet all of this diversity arises from embryonic skeletal elements that are each a very similar size at formation. In this review article, I survey what is and is not yet known of the development and evolution of skeletal proportion at multiple hierarchical levels of biological organization. These include the cellular parameters of skeletal elongation in the cartilage growth plate, genes associated with differential growth, and putative gene regulatory mechanisms that would allow both covariant and independent evolution of the forelimbs and hindlimbs and of individual limb segments. Although the genetic mechanisms that shape skeletal proportion are still largely unknown, and most of what is known is limited to mammals, it is becoming increasingly apparent that the diversity of bone lengths is an emergent property of a complex system that controls elongation of individual skeletal elements using a genetic toolkit shared by all.

SYNTHESIS OF POTENT ANTAGONISTS FOR THE NATRIURETIC PEPTIDE CLEARANCE RECEPTOR

Objectives: The objective of this research was to design and prepare natriuretic peptide clearance receptor (NPR-C) clearance receptor antagonists with potential therapy for achondroplasia, an autosomal dominant disorder that interferes with the synthesis of the cartilage growth plate of long bones.Methods: Peptides were synthesized by the standard solid-phase peptide synthesis (SPPS) protocol on Rink resin using the N-Fmoc/t-butyl protection methodology. Biological activity of NPR-C antagonists was assessed using ATDC5 cells.Results: SPPS rapidly generated many crude compounds with purities exceeding 80%. The synthesized ligands were further purified by liquid chromatography-mass spectrometry (LC-MS), and their identities were confirmed by MS and nuclear magnetic resonance. Ligands with nanomolar potencies were obtained.Conclusion: Structure-activity relationship studies resulted in a good selection of stable, low nanomolar, and linear NPR-C antagonists.