Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis （OA） is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor （EGFR） signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus （DMM） to induce OA in two mouse models with reduced EGFR activity, one with genetic modification （, was/＋ mice） and the other one with pharmacological inhibition （gefitinib treatment）. Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 （MMP13）, the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α （HIF2α）, a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation.

A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective treatment.Past animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical analyses.At trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

In vivo bone dynamic imaging of PTH's anabolic effect

Introduction Aging shifts bone remodeling toward a negative balance between bone formation and resorption,causing bone loss and increased fracture risk.Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass.While they are effective to prevent further bone loss,there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity.PTH,the only FDA-approved anabolic treatment for osteoporosis,greatly stimulates bone formation.Combined therapy of anti-resorptive treatments,such as alendronate(ALN),and PTH have been proposed and are expected to further increase bone mass.However,studies show conflicting results regarding the effectiveness

Traditional Agrodiversity Management:A Case Study of Central Himalayan Village Ecosystem

Environmental,biological,socio-cultural and economic status variation existing in the Central Himalaya have led to the evolution of diverse and unique traditional agroecosystems,crop species and livestock,which facilitate the traditional mountain farming societies to sustain themselves.Indigenous agroecosystems are highly site specific and differ from place to place,as they have evolved along divergent lines.For maintenance of traditional agrodiversity management the farmers of the Central Himalaya have evolved various types of crop rotations in consonance with the varied environmental conditions and agronomic requirements.In irrigated flat lands two crops are harvested in a year with negligible fallow period but in rainfed conditions if a cropping sequence is presumed to be starting after winter fallow phase then four major cropping seasons can be identified namely first kharif season(first crop season),first rabi season(second crop season),second kharif season(third crop season) and second rabi season(fourth crop season).Highest crop diversity is present in kharif season in comparison to rabi season.Traditionally the fields are left fallow after harvest of the second kharif season crop.Important characteristics of agrodiversity management are the use of bullocks for draughtpower,human energy as labour,crop residues as animal feed and animal waste mixed with forest litter as organic input to restore soil fertility levels.Women provide most of the human labour except for ploughing and threshing grain.The present study deals with assessment of traditional agrodiversity management such as(i) crop diversity,(ii) realized yield under the traditional practices and(iii) assess the differences of realized yields under sole and mixed cropping systems.It indicated that crop rotation is an important feature of the Central Himalayan village ecosystem which helps to continue the diversity of species grown,as are the distribution of crops in the growing period and the management of soil fertility.The cropping diversity existing and the sequences practiced by the traditional farmers seems to have achieved high degree of specialization and thus even when the yield/biomass variations are about 60%,the farmers continue to practice these sequences as they need to maintain diversity and synergistic relationships of crops in addition to manage the food and labour requirements for crop husbandry.Crop yields are generally higher in irrigated systems than rainfed systems and in sole cropping as compared with mixed cropping.However,gross biological and economic yields are higher in mixed cropping than sole cropping systems.