Ethanol extract of Annona muricata Linn fruit perform antidiabetic effect on type 2 diabetic mice through α-glucosidase inhibition

Objective:To explore the anti-diabetic effects and its underlying mechanism of Annona muricata Linn fruit ethanol extract(AME).Methods:Streptozotocin-induced type 2 diabetic(T2DM)mouse model was constructed.Those diabetic mice were randomly grouped and given 50 mg/kg acarbose or AME(200 mg/kg,100 mg/kg or 50 mg/kg)for four weeks.The body weight,postprandial blood glucose and glycosylated hemoglobin levels were measured during the administration.After the administration,a glucose tolerance test was performed,and the levels of triglycerides,cholesterol and low-density lipoproteins in mice were detected by biochemical test kits.The inhibitory activity of AME onα-glucosidase in vivo and in vitro was determined by enzyme inhibition tests.Results:AME significantly reduced weight gain,postprandial blood glucose,glycosylated hemoglobin and low-density lipoprotein levels in T2DM mice;enhanced glucose tolerance and pancreaticβ-cell function of T2DM mice;inhibitedα-glucosidase activity in mouse intestine in an noncompetitive manner.Conclusion:AME may noncompetitive inhibitα-glucosidase activity and reduce postprandial glucose intake to achieve a therapeutic and regulatory effect on type 2 diabetes.

α-Glucosidase Inhibition by New Schiff Base Complexes of Zn(II)

There are many reports that divalent alkaline earth, first-row transition metals, and Zn(II) ions have α-glucosidase inhibitory effects. Cu(II) and Zn(II) ions, in particular, have strong α-glucosidase inhibitory effects. Several Schiff bases also display α-glucosidase inhibitory effects. In this study, we focused on safe and highly effective complexes including Zn(II) ion. We prepared and characterized the Zn(II) complexes with four different Schiff bases (N-salicylidene-β-alanine (N-sβ), N-N’-bis (salicylidene) ethylenediamine (N-bsE), N, N’-bis (salicylidene)-phenylenediamine (N-bsP), and 1-[(2-dimethylaminoethylimino) methyl]naphtholate (DMN)) and investigated their α-glucosidase inhibitory effects in vitro, using α-glycosidases from Saccharomyces sp. and rat small intestine, and in vivo, using a sucrose tolerance test. The Zn(II) complexes with DMN showed the highest in vitro and in vivo α-glucosidase inhibitory effects in this study.

Blood glucose-lowering activity of protocatechuic acid is mediated by inhibiting a-glucosidase

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.

Structural characterizations andα-glucosidase inhibitory activities of four Lepidium meyenii polysaccharides with different molecular weights

Four polysaccharides(MCPa,MCPb,MCPc,MCPd)were obtained from Lepidium meyenii Walp.Their structures were characterized by chemical and instrumental methods including total sugar,uronic acid and protein content determi-nation,UV,IR and NMR spectroscopy,as well as monosaccharide composition determination and methylation analy-ses.Four polysaccharides were a group of glucans with different molecular weights ranging from 3.12 to 14.4 kDa,and shared a similar backbone chain consisting of(1→4)-glucose linkages with branches attached to C-3 and C-6.Furthermore,bioactivity assay showed that MCPs had concentration-dependent inhibitory activity onα-glucosidase.MCPb(Mw=10.1 kDa)and MCPc(Mw=5.62 kDa)with moderate molecular weights exhibited higher inhibitory activ-ity compared with MCPa and MCPd.

Inhibition of protein degradation increases the Bt protein concentration in Bt cotton

Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.

Heterointerface Engineering-Induced Oxygen Defects for the Manganese Dissolution Inhibition in Aqueous Zinc Ion Batteries

Manganese-based material is a prospective cathode material for aqueous zinc ion batteries(ZIBs)by virtue of its high theoretical capacity,high operating voltage,and low price.However,the manganese dissolution during the electrochemical reaction causes its electrochemical cycling stability to be undesirable.In this work,heterointerface engineering-induced oxygen defects are introduced into heterostructure MnO_(2)(δa-MnO_(2))by in situ electrochemical activation to inhibit manganese dissolution for aqueous zinc ion batteries.Meanwhile,the heterointerface between the disordered amorphous and the crystalline MnO_(2)ofδa-MnO_(2)is decisive for the formation of oxygen defects.And the experimental results indicate that the manganese dissolution ofδa-MnO_(2)is considerably inhibited during the charge/discharge cycle.Theoretical analysis indicates that the oxygen defect regulates the electronic and band structure and the Mn-O bonding state of the electrode material,thereby promoting electron transport kinetics as well as inhibiting Mn dissolution.Consequently,the capacity ofδa-MnO_(2)does not degrade after 100 cycles at a current density of 0.5 Ag^(-1)and also 91%capacity retention after 500cycles at 1 Ag^(-1).This study provides a promising insight into the development of high-performance manganese-based cathode materials through a facile and low-cost strategy.

Growth and inhibition of zinc anode dendrites in Zn-air batteries:Model and experiment

Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active material Zn.However,the Zn anode also leads to many challenges,including dendrite growth,deformation,and hydrogen precipitation self-corrosion.In this context,Zn dendrite growth has a greater impact on the cycle lives.In this dissertation,a dendrite growth model for a Zn-air battery was established based on electrochemical phase field theory,and the effects of the charging time,anisotropy strength,and electrolyte temperature on the morphology and growth height of Zn dendrites were studied.A series of experiments was designed with different gradient influencing factors in subsequent experiments to verify the theoretical simulations,including elevated electrolyte temperatures,flowing electrolytes,and pulsed charging.The simulation results show that the growth of Zn dendrites is controlled mainly by diffusion and mass transfer processes,whereas the electrolyte temperature,flow rate,and interfacial energy anisotropy intensity are the main factors.The experimental results show that an optimal electrolyte temperature of 343.15 K,an optimal electrolyte flow rate of 40 ml·min^(-1),and an effective pulse charging mode.

Antioxidant,antimicrobial,and α-glucosidase inhibitory activities of saponin extracts from walnut(Juglans regia L.) leaves

Objective:To investigate the relationship between triterpenoid saponin content and antioxidant,antimicrobial,and α-glucosidase inhibitory activities of 70%ethanolic,butanolic,aqueous,supernate and precipitate extracts of Juglans regia leaves.Methods:Triterpenoid saponins of different Juglans regia leaf extracts were measured by the vanillin method.Antioxidant activity was evaluated against DPPH and ABTS free radicals.We also assessed α-glucosidase inhibitory and antimicrobial activities of the leaf extracts.Pearson’s correlation coefficient was evaluated to determine the correlation between the saponin content and biological activities.Results:The butanolic extract was most effective against DPPH with an IC50of 6.63μg/mL,while the aqueous extract showed the highest scavenging activity against ABTS free radical with an IC50of 42.27μg/mL.Pearson’s correlation analysis indicated a strong negative correlation (r=-0.956) between DPPH radical scavenging activity (IC50) and the saponin content in the samples examined.In addition,the aqueous extract showed the best α-glucosidase inhibitory activity compared with other extracts.All the extracts had fair antibacterial activity against Bacillus subtilis,Escherichia coli,and Klebsiella pneumoniae except for the aqueous extract.Conclusions:Juglans regia extracts show potent antioxidant,antimicrobial,and α-glucosidase inhibitory activities.There is a correlation between saponin levels in Juglans regia leaf extracts and the studied activities.However,additional research is required to establish these relationships by identifying the specific saponin molecules responsible for these activities and elucidating their mechanisms of action.

Sensitivity of Commercial Enzyme Inhibition Colorimetric Pesticide Residue Rapid Test Kit to a Variety of Pesticides

[Objectives]To fully understand the quality of commercial enzyme inhibition-colorimetric pesticide residue rapid detection kits,so that they can play a greater role in the detection and supervision of agricultural products.[Methods]The sensitivity of 28 kinds of pesticides was determined by using the commercially available enzyme inhibition colorimetric rapid detection kit with Hendu brand.[Results]There was a significant difference in the sensitivity of the kit to each pesticide,and the kit was more sensitive to dichlorvos among the 28 pesticides tested.The sensitivity to methyl isosalifos,dimethoate,isocarbophos,fenthion and phorate was poor,and the sensitivity to quinalphos was different between 3.0 and 2.5 mL.[Conclusions]The large difference of the sensitivity of the enzyme inhibition-colorimetric rapid detection kit for pesticide residues to different kits is a reason for the false positive and false negative test results of the kit,which needs to be considered by relevant personnel.

Alleviated photoinhibition on nitrification in the Indian Sector of the Southern Ocean

Nitrification,a central process in the marine nitrogen cycle,produces regenerated nitrate in the euphotic zone and emits N_(2)O,a potent greenhouse gas as a by-product.The regulatory mechanisms of nitrification in the Southern Ocean,which is a critical region for CO_(2)sequestration and radiative benefits,remain poorly understood.Here,we investigated the in situ and dark nitrification rates in the upper 500 m and conducted substrate kinetics experiments across the Indian Sector in the Cosmonaut and Cooperation seas in the late austral summer.Our findings indicate that light inhibition of nitrification decreases exponentially with depth,exhibiting a light threshold of 0.53%photosynthetically active radiation.A positive relationship between dark nitrification and apparent oxygen utilization suggests a dependence on substrate availability from primary production.Importantly,an increased NH_(4)^(+) supply can act as a buffer against photo-inhibitory damage.Globally,substrate affinity(α)increases with depth and transitions from light to dark,decreases with increasing ambient NH_(4)^(+)and exhibits a latitudinal distribution,reflecting substrate utilization strategies.We also reveal that upwelling in Circumpolar Deep Water(CDW)stimulates nitrification through the introduction of potentially higher iron and deep diverse nitrifying microorganisms with higherα.We conclude that although light is the primary limiting factor for nitrification in summer,coupling between substrate availability and CDW upwelling can overcome this limitation,thereby alleviating photoinhibition by up to 45%±5.3%.

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

Determination of total flavonoids content in buckwheat and inhibition of α-amylase activity

Diabetes is one of the most difficult chronic diseases to cure in the world,which seriously affects people’s health and quality of life.Flavonoids in buckwheat can regulate blood glucose levels by inhibitingα-amylase activity.Therefore,sweet buckwheat produced in Inner Mongolia was used as the research object,and buckwheat fl avonoids were extracted by ultrasonic-assisted extraction method.Total fl avonoids content was determined by ultraviolet-visible spectrophotometry.With acarbose as the positive control,the inhibition test ofα-amylase was carried out by DNS colorimetry to study the inhibition behavior of fl avonoids onα-amylase activity.The results showed that the extraction process of flavonoids was stable and reliable,and the established method for the determination of flavonoids was simple,accurate and reproducible.The total flavonoids content of buckwheat samples was 2.706 mg/g,buckwheat total fl avonoids extraction solution had an inhibitory eff ect onα-amylase,and its median inhibition concentration(IC_(50))was 38.53 mg/mL.The results of this experiment provide a technical reference for the development and utilization of fl avonoids in Inner Mongolia sweet buckwheat,and provide a theoretical reference for the development and application of flavonoid-rich hypoglycemic food.

Role of TSH Inhibition Therapy in the Postoperative Management of Patients with Differentiated Thyroid Cancer

Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.

Efficiency of Oryza punctata extract on glucose regulation: Inhibition of α-amylase and α-glucosidase activities

Red rice(Oryza punctata) is a type of unpolished rice which has higher nutritional value compared to white rice or even polished rice. Owing to higher nutritive content and metabolites, dieticians strongly advise red rice for peoples with metabolic disorders including diabetics. However, the mechanism of action and contents of secondary metabolites in Indian red rice variety not reported scientifically. Therefore, the present study aimed to evaluate its mechanism of action through inhibitory effect of α-amylase and α-glucosidase. Initially, the whole grain of red rice was macerated with methanol at room temperature for 2 weeks. Then, the dried and powdered, samples at different concentrationfi(2.5, 10, 40, and 80 μg/m L) were employed to nd out in vitro inhibitory effects on α-amylase and α-glucosidase. In addition, an enzyme kinetics of effective extract was calculated by Line-weaver Burk(LWB) plot analysis. Moreover,the valuable metabolites in the efficient methanolic extract were quantified using high performance liquid chromatography(HPLC). The results demonstrated that red rice methanolic extract(RRMEt) possess strong inhibitory activity onα-amylase and α-glucosidase compared with acarbose(P < 0.01). The IC50 values of RRMEt was found to be 29.7 ±7.43 μg/m L for α-amylase and 20.4 ± 0.25 μg/m L for α-glucosidase. LWB indicated that RRMEt is an uncompetitive inhibitor. Further, HPLC analysis revealed protocatechuic acid, catechin, and chlorogenic acids were more abundant in RRMEt among the fourteen metabolites. We conclude, the efficiency of enzyme inhibition through the influence of phenolic compounds in RRMEt.

Inhibition of α-amylase and α-glucosidase activities by ethanolic extract of Telfairia occidentalis (fluted pumpkin) leaf

Objective:To investigate the inhibitory effect of Telfairia occidentalis Hook f.(Curcubitaceae)(T.occidentalis)leaf on key enzyme linked to type-2 diabetes(α-amylase andα-glucosidase)as well as assess the effect of blanching(a commonly practiced food processing technique)of the vegetable on these key enzymes.Methods:Fresh leaves of T.occidentalis were blanched in hot water for 10 minutes,and the extracts of both the fresh and blanched vegetables were prepared and used for subsequent analysis.The inhibitory effect of the extract onα-amylase andα-glucosidase activities as well as some antioxidant parameter was determined in vitro.Results:The result revealed that unprocessed T.occidentalis leaf reduce Fe^(3+)to Fe^(2+)and also inhibitedα-amylase andα-glucosidase activities in a dose dependent manner.However,blanching of the leafy vegetables caused a significant(P<0.05)increase in the antioxidant properties but decrease their ability to inhibitα-amylase andα-glucosidase activities.Conclusions:This antioxidant properties and enzyme inhibition could be part of the mechanism by which they are used in the treatment/prevention of type-2 diabetes.However,the blanched vegetable reduces their ability to inhibit bothα-amylase andα-glucosidase activity in vitro.

Total phenolic compounds,antioxidant potential and α-glucosidase inhibition by Tunisian Euphorbia paralias L.

Objective:To examine the potential antioxidant and anti-α-glucosidase inhibitory activities of Tunisian Euphorbia paralias L.leaves and stems extracts and their composition of total polyphenol and flavonoids.Methods:The different samples were tested for their antiradical activities by using 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)and 1,1-diphenyl-2-picrylhydrazyl(DPPH)assays.Inα-glucosidase activity,α-glucosidase(0.3 IU/mL)and substrate,2500μmol/L p-nitrophenylα-D-glucopyranoside were used;absorbance was registered at 405 nm.Results:The leaves acetonic extract exhibited the strongestα-glucosidase inhibition[IC_(50)=(0.0035±0.001)μg/mL],which was 20-fold more active than the standard product(acarbose)[IC_(50)=(0.07±0.01)μg/mL].Acetonic extract of the leaves exhibited the highest quantity of total phenolic[(95.54±0.04)μg gallic acid equivalent/mg]and flavonoid[(55.16±0.25)μg quercetin equivalent/mg].The obtained findings presented also that this extract was detected with best antioxidant capacity[IC_(50)=(0.015±0.01)μg/mL]against DPPH and a value of IC_(50)equal to(0.02±0.01)μg/mL against ABTS.Positive relationship between polyphenolic content of the tested Euphorbia paralias L.leaves and stems extracts and its antioxidant activity(DPPH and ABTS)was detected.Elevated positive linear correlation was got between ABTS and total phenolic(R^(2)=0.751).Conclusions:The findings clearly demonstrate that the use of a polar solvent enables extraction of significant quantities of phenol compounds and flavonoids.

α-Glucosidase Inhibitors from Glycyrrhiza uralensis Fisch.

Aim To screen for α-glucosidase inhibitor from Glyeyrrhiza uralensis Fisch.. Methods Glycyrrhizic acid, glycyrrhetinic acid, flavonoids of glycyrrhiza, alkaloids of glycyrrhiza, and glycyrrhiza polysaccharides were isolated from the root of Glycyrrhiza uralensis Fisch. respectively. Three compounds were isolated from the flavonoids of glycyrrhiza as guided by the α-glucosidase inhibitory test in vitro. Moreover, the characteristics of inhibitory kinetics of glycyrol and glycyrrhetinic acid were investi- gated. Results The flavonoids of glycyrrhiza and glycyrrhetinic acid had the strongest α-glucosidase inhibitory activity. Glycyrol,β-sitosterol and liquifitin were isolated and identified. Glycyrol was a fast- binding, reversible, noncompetitive α-glucosidase inhibitor, showing IC50 at 0.26 μg·mL^-1 Glycyrrhetinic acid was a fast-binding, irreversible α-glucosidase inhibitor, showing IC50 at 102.4 μg·mL^-1. Conclusion Glycyrol is an effective α-glucosidase inhibitor.

Effects of α-glucosidase Inhibitors on the Function of Mulberry Leaf Extract as an Additive in Feedstuff

The mulberry juice contains high concentrations of α-glucosidase inhibitors that affect glycometabolism and cause diarrhea in animals, thereby affecting the de-velopment and application of mulberry （Morus alba L.） as feedstuff resources. ln this study, the effects of mulberry leaf extract with and without removal of mulberry juice on starch metabolism were analyzed and compared. The results showed that mul-berry leaf extract with removal of mulberry juice exhibited significantly lower inhibi-tion rate on starch metabolism compared with mulberry leaf extract without removal of mulberry juice. ln animal feeding trials, piglet feedstuff was added with 10% mul-berry leaf powder; compared with mulberry leaf powder without removal of mulberry juice, experimental piglets fed with mulberry leaf powder with removal of mulberry juice exhibited significantly improved weight gain and significantyl reduced diarrhea rate.

New flavanone-monoterpene hybrids as α-glucosidase inhibitors from the root bark of Morus alba

Objective The Morus alba root bark is a well-known Chinese herbal medicine called Sang-Bai-Pi and has often been used to relieve the hyperglycemic symptom of diabetes patients.The current work aims to further explore its bioactive constituents with α-glucosidase inhibitory activity for the potential treatment of diabetes.Methods A combination of different separating techniques including routine column chromatograph and HPLC especially on chiral columns were applied for the isolation of target molecules,while comprehensive spectroscopic experiments comprising MS,NMR,ECD,etc.were carried out to complete the structural assignment.The anti-hyperglycemic property of the isolates was evaluated by an in vitro α-glucosidase inhibitory bioassay.Results Two pairs of new flavanone-monoterpene hybrid enantiomers were isolated and identified,and an interesting phenomenon of mutual transformation between these cometabolites were detected,which resulted in their regio-isomerization and enantiomerization.The bioassay results revealed remarkable α-glucosidase inhibitory activity for these fascinating molecules.Conclusions The Morus alba root bark is a rich source of bioactive flavonoid derivatives and deserves further investigations to develop new potential chemotherapies for diabetes control and treatment.

Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression

Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.