Flexible silicon solar cells with high power-to-weight ratios.

Silicon solar cells are a mainstay of commercialized photovoltaics, and further improving the power conversion efficiency of large-area and flexible cells remains an important research objective1,2. Here we report a combined approach to improving the power conversion efficiency of silicon heterojunction solar cells, while at the same time rendering them flexible. We use low-damage continuous-plasma chemical vapour deposition to prevent epitaxy, self-restoring nanocrystalline sowing and vertical growth to develop doped contacts, and contact-free laser transfer printing to deposit low-shading grid lines. High-performance cells of various thicknesses (55-130 µm) are fabricated, with certified efficiencies of 26.06% (57 µm), 26.19% (74 µm), 26.50% (84 µm), 26.56% (106 µm) and 26.81% (125 µm). The wafer thinning not only lowers the weight and cost, but also facilitates the charge migration and separation. It is found that the 57-µm flexible and thin solar cell shows the highest power-to-weight ratio (1.9 W g-1) and open-circuit voltage (761 mV) compared to the thick ones. All of the solar cells characterized have an area of 274.4 cm2, and the cell components ensure reliability in potential-induced degradation and light-induced degradation ageing tests. This technological progress provides a practical basis for the commercialization of flexible, lightweight, low-cost and highly efficient solar cells, and the ability to bend or roll up crystalline silicon solar cells for travel is anticipated.

Perovskite/silicon tandem solar cells with bilayer interface passivation.

Two-terminal monolithic perovskite/silicon tandem solar cells demonstrate huge advantages in power conversion efficiency compared with their respective single-junction counterparts1,2. However, suppressing interfacial recombination at the wide-bandgap perovskite/electron transport layer interface, without compromising its superior charge transport performance, remains a substantial challenge for perovskite/silicon tandem cells3,4. By exploiting the nanoscale discretely distributed lithium fluoride ultrathin layer followed by an additional deposition of diammonium diiodide molecule, we have devised a bilayer-intertwined passivation strategy that combines efficient electron extraction with further suppression of non-radiative recombination. We constructed perovskite/silicon tandem devices on a double-textured Czochralski-based silicon heterojunction cell, which featured a mildly textured front surface and a heavily textured rear surface, leading to simultaneously enhanced photocurrent and uncompromised rear passivation. The resulting perovskite/silicon tandem achieved an independently certified stabilized power conversion efficiency of 33.89%, accompanied by an impressive fill factor of 83.0% and an open-circuit voltage of nearly 1.97 V. To the best of our knowledge, this represents the first reported certified efficiency of a two-junction tandem solar cell exceeding the single-junction Shockley-Queisser limit of 33.7%.

Silicon heterojunction back contact solar cells by laser patterning.

Back contact silicon solar cells, valued for their aesthetic appeal by removing grid lines on the sunny side, find applications in buildings, vehicles and aircrafts, enabling self-power generation without compromising appearance1-3. Patterning techniques arrange contacts on the shaded side of the silicon wafer, offering benefits for light incidence as well. However, the patterning process complicates production and causes power loss. Here we employ lasers to streamline back contact solar cell fabrication and enhance power conversion efficiency. Our approach produces the first silicon solar cell to exceed 27% efficiency. Hydrogenated amorphous silicon layers are deposited on the wafer for surface passivation and collection of light-generated carriers. A dense passivating contact, diverging from conventional technology practice, is developed. Pulsed picosecond lasers at different wavelengths are used to create back contact patterns. The developed approach is a streamlined process for producing high-performance back contact silicon solar cells, with a total effective processing time of about one-third that of emerging mainstream technology. To meet terawatt demand, we develop rare indium-less cells at 26.5% efficiency and precious silver-free cells at 26.2% efficiency. The integration of solar solutions in buildings and transportation is poised to expand with these technological advancements.

Global characterization of somatic mutations and DNA methylation changes during vegetative propagation in strawberries.

Somatic mutations arise and accumulate during tissue culture and vegetative propagation, potentially affecting various traits in horticultural crops, but their characteristics are still unclear. Here, somatic mutations in regenerated woodland strawberry derived from tissue culture of shoot tips under different conditions and 12 cultivated strawberry individuals are analyzed by whole genome sequencing. The mutation frequency of single nucleotide variants is significantly increased with increased hormone levels or prolonged culture time in the range of 3.3 × 10-8-3.0 × 10-6 mutations per site. CG methylation shows a stable reduction (0.71%-8.03%) in regenerated plants, and hypoCG-DMRs are more heritable after sexual reproduction. A high-quality haplotype-resolved genome is assembled for the strawberry cultivar "Beni hoppe." The 12 "Beni hoppe" individuals randomly selected from different locations show 4731-6005 mutations relative to the reference genome, and the mutation frequency varies among the subgenomes. Our study has systematically characterized the genetic and epigenetic variants in regenerated woodland strawberry plants and different individuals of the same strawberry cultivar, providing an accurate assessment of somatic mutations at the genomic scale and nucleotide resolution in plants.

Transcription factor FveMYB117a inhibits axillary bud outgrowth by regulating cytokinin homeostasis in woodland strawberry.

Shoot branching affects plant architecture. In strawberry (Fragaria L.), short branches (crowns) develop from dormant axillary buds to form inflorescences and flowers. While this developmental transition contributes greatly to perenniality and yield in strawberry, its regulatory mechanism remains unclear and understudied. In the woodland strawberry (Fragaria vesca), we identified and characterized 2 independent mutants showing more crowns. Both mutant alleles reside in FveMYB117a, a R2R3-MYB transcription factor gene highly expressed in shoot apical meristems, axillary buds, and young leaves. Transcriptome analysis revealed that the expression of several cytokinin pathway genes was altered in the fvemyb117a mutant. Consistently, active cytokinins were significantly increased in the axillary buds of the fvemyb117a mutant. Exogenous application of cytokinin enhanced crown outgrowth in the wild type, whereas the cytokinin inhibitors suppressed crown outgrowth in the fvemyb117a mutant. FveMYB117a binds directly to the promoters of the cytokinin homeostasis genes FveIPT2 encoding an isopentenyltransferase and FveCKX1 encoding a cytokinin oxidase to regulate their expression. Conversely, the type-B Arabidopsis response regulators FveARR1 and FveARR2b can directly inhibit the expression of FveMYB117a, indicative of a negative feedback regulation. In conclusion, we identified FveMYB117a as a key repressor of crown outgrowth by inhibiting cytokinin accumulation and provide a mechanistic basis for bud fate transition in an herbaceous perennial plant.

Genomic analyses reveal dead-end hybridization between two deeply divergent kiwifruit species rather than homoploid hybrid speciation.

Despite the importance of hybridization in evolution, the evolutionary consequence of homoploid hybridizations in plants remains poorly understood. Specially, homoploid hybridization events have been rarely documented due to a lack of genomic resources and methodological limitations. Actinidia zhejiangensis was suspected to have arisen from hybridization of Actinidia eriantha and Actinidia hemsleyana or Actinidia rufa. However, this species was very rare in nature and exhibited sympatric distribution with its potential parent species, which implied it might be a spontaneous hybrid of ongoing homoploid hybridization. Here, we illustrate the dead-end homoploid hybridization and genomic basis of isolating barriers between A. eriantha and A. hemsleyana through whole genome sequencing and population genomic analyses. Chromosome-scale genome assemblies of A. zhejiangensis and A. hemsleyana were generated. The chromosomes of A. zhejiangensis are confidently assigned to the two haplomes, and one of them originates from A. eriantha and the other originates from A. hemsleyana. Whole genome resequencing data reveal that A. zhejiangensis are mainly F1 hybrids of A. hemsleyana and A. eriantha and gene flow initiated about 0.98 million years ago, implying both strong genetic barriers and ongoing hybridization between these two deeply divergent kiwifruit species. Five inversions containing genes involved in pollen germination and pollen tube growth might account for the fertility breakdown of hybrids between A. hemsleyana and A. eriantha. Despite its distinct morphological traits and long recurrent hybrid origination, A. zhejiangensis does not initiate speciation. Collectively, our study provides new insights into homoploid hybridization in plants and provides genomic resources for evolutionary and functional genomic studies of kiwifruit.

Karrikin Signaling Acts Parallel to and Additively with Strigolactone Signaling to Regulate Rice Mesocotyl Elongation in Darkness.

Seedling emergence in monocots depends mainly on mesocotyl elongation, requiring coordination between developmental signals and environmental stimuli. Strigolactones (SLs) and karrikins are butenolide compounds that regulate various developmental processes; both are able to negatively regulate rice (Oryza sativa) mesocotyl elongation in the dark. Here, we report that a karrikin signaling complex, DWARF14-LIKE (D14L)-DWARF3 (D3)-O. sativa SUPPRESSOR OF MAX2 1 (OsSMAX1) mediates the regulation of rice mesocotyl elongation in the dark. We demonstrate that D14L recognizes the karrikin signal and recruits the SCFD3 ubiquitin ligase for the ubiquitination and degradation of OsSMAX1, mirroring the SL-induced and D14- and D3-dependent ubiquitination and degradation of D53. Overexpression of OsSMAX1 promoted mesocotyl elongation in the dark, whereas knockout of OsSMAX1 suppressed the elongated-mesocotyl phenotypes of d14l and d3 OsSMAX1 localizes to the nucleus and interacts with TOPLESS-RELATED PROTEINs, regulating downstream gene expression. Moreover, we showed that the GR24 enantiomers GR245DS and GR24 ent-5DS specifically inhibit mesocotyl elongation and regulate downstream gene expression in a D14- and D14L-dependent manner, respectively. Our work revealed that karrikin and SL signaling play parallel and additive roles in modulating downstream gene expression and negatively regulating mesocotyl elongation in the dark.

Efficient non-fullerene organic solar cells employing aqueous solution-processed MoO3as a hole-transporting layer.

Organic solar cell (OSC) has drawn considerable interest in recent decades owing to their advantages of light weight, flexible, large area and potentially low-cost. Employing an appropriate hole-transporting layer (HTL) into an OSC device has been proved as an efficient method to obtain high efficiency OSC due to the enhancement of the hole transporting and extraction of the device. In this work, aqueous solution-processed MoO3(s-MoO3) thin films were employed as HTLs to construct non-fullerene PM6:Y6 OSCs. The s-MoO3thin film was prepared by using an aqueous solution process from an isopolymolybdate [NH4]6Mo7O24.4H2O precursor followed by thermal annealing treatment to convert the precursor to MoO3. The s-MoO3HTL based PM6:Y6 device demonstrates a power conversion efficiency of 15.75%, which is 38% improved than that of the device with thermally evaporated-MoO3as HTL and 8% improved than that of the device with PEDOT:PSS as HTL. The enhancement of the device performance could be attributed to the enhanced hole mobility and better band matching of the s-MoO3HTL. Moreover, the s-MoO3HTL based PM6:Y6 device exhibited higher device stability than those of the reference devices. Our finding indicates that this s-MoO3film has great potential as efficient HTL for high performance non fullerene OSCs.

Integrated Transcriptomic and Metabolomics Analysis of the Root Responses of Orchardgrass to Submergence Stress.

Submergence stress can severely affect plant growth. Orchardgrass (Dactylis glomerata L.) is an important forage grass, and the molecular mechanisms of orchardgrass to submergence stress are not well understood. The roots of the flood-tolerant cultivar "Dian Bei" were harvested at 0 h, 8 h and 24 h of submergence stress. The combined transcriptomic and metabolomic analyses showed that ß-alanine metabolism, flavonoid biosynthesis, and biosynthesis of amino acid pathways were significantly enriched at 8 h and 24 h of submergence stress and were more pronounced at 24 h. Most of the flavonoid biosynthesis-related genes were down-regulated for the synthesis of metabolites such as naringenin, apigenin, naringin, neohesperidin, naringenin chalcone, and liquiritigenin in response to submergence stress. Metabolites such as phenylalanine, tyrosine, and tryptophan were up-regulated under stress. The predominant response of flavonoid and amino acids biosynthesis to submergence stress suggests an important role of these pathways in the submergence tolerance of orchardgrass.

Enhanced Performance of Flexible Organic Photovoltaics Based on MoS2 Micro-Nano Array.

In this work, we investigated the influence of MoS2 functioning as an electron transport layer (ETL) on the inverted flexible organic photovoltaics (FOPVs). Three ETLs, including MoS2, lithium quinolate (Liq), and a MoS2/Liq bilayer, were evaporated onto ITO-integrated polyethylene terephthalate substrates (PET-ITO), and the properties of transmittance, water contact angle, and reflectivity of the films were analyzed. The results revealed that MoS2 was helpful to improve the lipophilicity of the surface of the ETL, which was conducive to the deposition of the active layer. In addition, the reflectivity of MoS2 to the light ranging from 400 to 600 nm was the largest among the pristine PET-ITO substrate and the PET-ITO coated with three ETLs, which promoted the efficient use of the light. The efficiency of the FOPV with MoS2/Liq ETL was 73% higher than that of the pristine device. This was attributed to the nearly two-fold amplification of the MoS2 array to the light field, which promoted the FOPV to absorb more light. Moreover, the efficiency of the FOPV with MoS2 was maintained under different illumination angles and bending angles. The results demonstrate the promising applications of MoS2 in the fabrication of FOPVs.

OsWR2 recruits HDA704 to regulate the deacetylation of H4K8ac in the promoter of OsABI5 in response to drought stress.

Drought stress is a major environmental factor that limits the growth, development, and yield of rice (Oryza sativa L.). Histone deacetylases (HDACs) are involved in the regulation of drought stress responses. HDA704 is an RPD3/HDA1 class HDAC that mediates the deacetylation of H4K8 (lysine 8 of histone H4) for drought tolerance in rice. In this study, we show that plants overexpressing HDA704 (HDA704-OE) are resistant to drought stress and sensitive to abscisic acid (ABA), whereas HDA704 knockout mutant (hda704) plants displayed decreased drought tolerance and ABA sensitivity. Transcriptome analysis revealed that HDA704 regulates the expression of ABA-related genes in response to drought stress. Moreover, HDA704 was recruited by a drought-resistant transcription factor, WAX SYNTHESIS REGULATORY 2 (OsWR2), and co-regulated the expression of the ABA biosynthesis genes NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3), NCED4, and NCED5 under drought stress. HDA704 also repressed the expression of ABA-INSENSITIVE 5 (OsABI5) and DWARF AND SMALL SEED 1 (OsDSS1) by regulating H4K8ac levels in the promoter regions in response to polyethylene glycol 6000 treatment. In agreement, the loss of OsABI5 function increased resistance to dehydration stress in rice. Our results demonstrate that HDA704 is a positive regulator of the drought stress response and offers avenues for improving drought resistance in rice.

A genome-wide survey of copy number variations reveals an asymmetric evolution of duplicated genes in rice.

BACKGROUND: Copy number variations (CNVs) are an important type of structural variations in the genome that usually affect gene expression levels by gene dosage effect. Understanding CNVs as part of genome evolution may provide insights into the genetic basis of important agricultural traits and contribute to the crop breeding in the future. While available methods to detect CNVs utilizing next-generation sequencing technology have helped shed light on prevalence and effects of CNVs, the complexity of crop genomes poses a major challenge and requires development of additional tools. RESULTS: Here, we generated genomic and transcriptomic data of 93 rice (Oryza sativa L.) accessions and developed a comprehensive pipeline to call CNVs in this large-scale dataset. We analyzed the correlation between CNVs and gene expression levels and found that approximately 13% of the identified genes showed a significant correlation between their expression levels and copy numbers. Further analysis showed that about 36% of duplicate pairs were involved in pseudogenetic events while only 5% of them showed functional differentiation. Moreover, the offspring copy mainly contributed to the expression levels and seemed more likely to become a pseudogene, whereas the parent copy tended to maintain the function of ancestral gene. CONCLUSION: We provide a high-accuracy CNV dataset that will contribute to functional genomics studies and molecular breeding in rice. We also showed that gene dosage effect of CNVs in rice is not exponential or linear. Our work demonstrates that the evolution of duplicated genes is asymmetric in both expression levels and gene fates, shedding a new insight into the evolution of duplicated genes.

Morphological and molecular response mechanisms of the root system of different Hemarthria compressa species to submergence stress.

Introduction: The severity of flood disasters is increasing due to climate change, resulting in a significant reduction in the yield and quality of forage crops worldwide. This poses a serious threat to the development of agriculture and livestock. Hemarthria compressa is an important high-quality forage grass in southern China. In recent years, frequent flooding has caused varying degrees of impacts on H. compressa and their ecological environment. Methods: In this study, we evaluated differences in flooding tolerance between the root systems of the experimental materials GY (Guang Yi, flood-tolerant) and N1291 (N201801291, flood-sensitive). We measured their morphological indexes after 7 d, 14 d, and 21 d of submergence stress and sequenced their transcriptomes at 8 h and 24 h, with 0 h as the control. Results: During submergence stress, the number of adventitious roots and root length of both GY and N1291 tended to increase, but the overall growth of GY was significantly higher than that of N1291. RNA-seq analysis revealed that 6046 and 7493 DEGs were identified in GY-8h and GY-24h, respectively, and 9198 and 4236 DEGs in N1291-8h and N1291-24h, respectively, compared with the control. The GO and KEGG enrichment analysis results indicated the GO terms mainly enriched among the DEGs were oxidation-reduction process, obsolete peroxidase reaction, and other antioxidant-related terms. The KEGG pathways that were most significantly enriched were phenylpropanoid biosynthesis, plant hormone signal transduction etc. The genes of transcription factor families, such as C2H2, bHLH and bZIP, were highly expressed in the H. compressa after submergence, which might be closely related to the submergence adaptive response mechanisms of H. compressa. Discussion: This study provides basic data for analyzing the molecular and morphological mechanisms of H. compressa in response to submergence stress, and also provides theoretical support for the subsequent improvement of submergence tolerance traits of H. compressa.

Crop detection technologies, mechanical weeding executive parts and working performance of intelligent mechanical weeding: a review.

Weeding is a key link in agricultural production. Intelligent mechanical weeding is recognized as environmentally friendly, and it profoundly alleviates labor intensity compared with manual hand weeding. While intelligent mechanical weeding can be implemented only when a large number of disciplines are intersected and integrated. This article reviewed two important aspects of intelligent mechanical weeding. The first one was detection technology for crops and weeds. The contact sensors, non-contact sensors and machine vision play pivotal roles in supporting crop detection, which are used for guiding the movements of mechanical weeding executive parts. The second one was mechanical weeding executive part, which include hoes, spring teeth, fingers, brushes, swing and rotational executive parts, these parts were created to adapt to different soil conditions and crop agronomy. It is a fact that intelligent mechanical weeding is not widely applied yet, this review also analyzed the related reasons. We found that compared with the biochemical sprayer, intelligent mechanical weeding has two inevitable limitations: The higher technology cost and lower working efficiency. And some conclusions were commented objectively in the end.

Pip5k1γ promotes anabolism of nucleus pulposus cells and intervertebral disc homeostasis by activating CaMKII-Ampk pathway in aged mice.

Degenerative disc disease (DDD) represents a significant global health challenge, yet its underlying molecular mechanisms remain elusive. This study aimed to investigate the role of type 1 phosphatidylinositol 4-phosphate 5-kinase (Pip5k1) in intervertebral disc (IVD) homeostasis and disease. All three Pip5k1 isoforms, namely Pip5k1α, Pip5k1ß, and Pip5k1γ, were detectable in mouse and human IVD tissues, with Pip5k1γ displaying a highest expression in nucleus pulposus (NP) cells. The expression of Pip5k1γ was significantly down-regulated in the NP cells of aged mice and patients with severe DDD. To determine whether Pip5k1γ expression is required for disc homeostasis, we generated a Pip5k1γfl/fl; AggrecanCreERT2 mouse model for the conditional knockout of the Pip5k1γ gene in aggrecan-expressing IVD cells. Our findings revealed that the conditional deletion of Pip5k1γ did not affect the disc structure or cellular composition in 5-month-old adult mice. However, in aged (15-month-old) mice, this deletion led to several severe degenerative disc defects, including decreased NP cellularity, spontaneous fibrosis and cleft formation, and a loss of the boundary between NP and annulus fibrosus. At the molecular level, the absence of Pip5k1γ reduced the anabolism of NP cells without markedly affecting their catabolic or anti-catabolic activities. Moreover, the loss of Pip5k1γ significantly dampened the activation of the protective Ampk pathway in NP cells, thereby accelerating NP cell senescence. Notably, Pip5k1γ deficiency blunted the effectiveness of metformin, a potent Ampk activator, in activating the Ampk pathway and mitigating lumbar spine instability (LSI)-induced disc lesions in mice. Overall, our study unveils a novel role for Pip5k1γ in promoting anabolism and maintaining disc homeostasis, suggesting it as a potential therapeutic target for DDD.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Brassinosteroid catabolic enzyme CYP734A129 regulates the morphologies of leaves and floral organs in woodland strawberry.

Brassinosteroids (BRs) play critical roles in plant growth and development and regulate many important agronomic traits. However, the functions of BRs in strawberry are unclear. This study identified two mutants, named P6 and R87, in woodland strawberry (Fragaria vesca) from EMS mutagenesis populations that exhibit narrow leaves, petals and sepals. Mapping by sequencing and genetic studies revealed that the F. vesca CYP734A129, encoding a putative BR catabolic enzyme, is the causative gene for both P6 and R87. Overexpression of CYP734A129 in both F. vesca and Arabidopsis causes a severe dwarf phenotype, and the BRI1-EMS-SUPPRESSOR 1 (BES1) protein is less abundant in the CYP734A129-overexpressing Arabidopsis seedlings. This suggests that CYP734A129 is functionally conserved with CYP734A1, as a BR-inactivating enzyme. Transcriptome analysis of young leaves revealed that four BR biosynthetic genes were significantly downregulated in P6 (cyp734a129), and photosynthesis-related genes were highly enriched among the up-regulated genes in P6 compared to the wild type. This further supports that CYP734A129 inactivates BRs in F. vesca. Furthermore, we showed that mutations in CYP734A129 do not affect fruit shape and color during ripening in strawberry. Overall, our results suggest that F. vesca CYP734A129 is a BR catabolic enzyme, and provide insights into the roles of CYP734A129 in strawberry.

Osteoarthritis: pathogenic signaling pathways and therapeutic targets.

Osteoarthritis (OA) is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide. OA was believed to be caused by the wearing and tearing of articular cartilage, but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues, which leads to the histological and structural changes of the joint and ends up with the whole tissue dysfunction. Currently, there is no cure for OA, partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the disease. Therefore, a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development. In this review, we first summarize the epidemiology of OA, including its prevalence, incidence and burdens, and OA risk factors. We then focus on the roles and regulation of the pathological signaling pathways, such as Wnt/ß-catenin, NF-κB, focal adhesion, HIFs, TGFß/ΒΜP and FGF signaling pathways, and key regulators AMPK, mTOR, and RUNX2 in the onset and development of OA. In addition, the roles of factors associated with OA, including MMPs, ADAMTS/ADAMs, and PRG4, are discussed in detail. Finally, we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA. Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies.

Pip5k1c Loss in Chondrocytes Causes Spontaneous Osteoarthritic Lesions in Aged Mice.

Osteoarthritis (OA) is the most common degenerative joint disease affecting the older populations globally. Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (Pip5k1c), a lipid kinase catalyzing the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), is involved in various cellular processes, such as focal adhesion (FA) formation, cell migration, and cellular signal transduction. However, whether Pip5k1c plays a role in the pathogenesis of OA remains unclear. Here we show that inducible deletion of Pip5k1c in aggrecan-expressing chondrocytes (cKO) causes multiple spontaneous OA-like lesions, including cartilage degradation, surface fissures, subchondral sclerosis, meniscus deformation, synovial hyperplasia, and osteophyte formation in aged (15-month-old) mice, but not in adult (7-month-old) mice. Pip5k1c loss promotes extracellular matrix (ECM) degradation, chondrocyte hypertrophy and apoptosis, and inhibits chondrocyte proliferation in the articular cartilage of aged mice. Pip5k1c loss dramatically downregulates the expressions of several key FA proteins, including activated integrin ß1, talin, and vinculin, and thus impairs the chondrocyte adhesion and spreading on ECM. Collectively, these findings suggest that Pip5k1c expression in chondrocytes plays a critical role in maintaining articular cartilage homeostasis and protecting against age-related OA.

Comparison of Kindlin-2 deficiency-stimulated osteoarthritis-like lesions induced by Prg4CreERT2 versus AggrecanCreERT2 transgene in mice.

Background: Genetically modified mice are the most useful tools for investigating the gene functions in articular cartilage biology and the pathogenesis of osteoarthritis. The AggrecanCreERT2 mice are one of the most reported mouse lines used for this purpose. The Prg4 (proteoglycan 4) gene encodes the lubricin protein and is expressed selectively in chondrocytes located at the superficial layer of the articular cartilage. While the Prg4GFPCreERT2 knock-in inducible-Cre transgenic mice were generated a while ago, so far, few studies have used this mouse line to perform gene functional studies in cartilage biology. Methods: We have recently reported that deleting the Fermt2 gene, which encodes the key focal adhesion protein Kindlin-2, in articular chondrocytes by using the AggrecanCreERT2 transgenic mice, results in spontaneous osteoarthritis (OA) lesions, which highly mimics the human OA pathologies. In this study, we have compared the Kindlin-2 deficiency-caused OA phenotypes induced by Prg4GFPCreERT2 with those caused by AggrecanCreERT2 using imaging and histological analyses. Results: We find that Kindlin-2 protein is deleted in about 75% of the superficial articular chondrocytes in the tamoxifen (TAM)-treated Prg4GFPCreERt2/+; Fermt2fl/fl mice compared to controls. At 6 months after TAM injections, the OARSI scores of AggrecanCreERT2/+; Fermt2fl/fl and Prg4GFPCreERt2/+; Fermt2fl/fl mice were 5 and 3, respectively. The knee joints histological osteophyte and synovitis scores were also significantly decreased in Prg4GFPCreERT2/+; Fermt2fl/fl mice compared to those in AggrecanCreERT2/+; Fermt2fl/fl mice. Furthermore, magnitudes of upregulation of the extracellular matrix-degrading enzymes Mmp13 and hypertrophic chondrocyte markers Col10a1 and Runx2 were decreased in Prg4GFPCreERT2/+; Fermt2fl/fl versus AggrecanCreERT2/+; Fermt2fl/fl mice. We finally examined the susceptibility of Prg4GFPCreERT2/+; Fermt2fl/fl mouse model to surgically induce OA lesions. The pathological features of OA in the TAM-DMM model exhibited significant enhancement in cartilage erosion, proteoglycan loss, osteophyte, and synovitis and an increase in OARSI score in articular cartilage compared with those in corn-oil DMM mice. Conclusion: Kindlin-2 loss causes milder OA-like lesions in Prg4GFPCreERT2/+;Fermt2fl/fl than in AggrecanCreERT2/+; Fermt2fl/fl mice. In contrast, Kindlin-2 loss similarly accelerates the destabilization of the medial meniscus-induced OA lesions in both mice.Translational Potential of this Article: Our study demonstrates that Prg4GFPCreERT2 is a useful tool for gene functional study in OA research. This study provides useful information for investigators to choose appropriate Cre mouse lines for their research in cartilage biology.