REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit anti-GAPDH	Abcam	Cat# ab9485; RRID: AB_307275
Rabbit anti-IL6ST	Abcam	Cat# ab283685
Rabbit anti-eGFP	Bioss	Cat# bs-2194R; RRID: AB_10881247
Rabbit anti-mCherry	Bioss	Cat# bs-41161R
Rabbit anti-TIMP1	Bioss	Cat# bs-0415R; RRID: AB_10856775
Rabbit anti-TIMP3	Abcam	Cat# ab277794
Rabbit anti-ADAMTS4	Bioss	Cat# bs-4191R; RRID: AB_11073215
Rabbit anti-ADAMTS5	Bioss	Cat# bs-3573R; RRID: AB_10856276
Rabbit anti-RUNX2	Bioss	Cat# bs-1134R; RRID: AB_10856062
Rabbit anti-MMP1	Bioss	Cat# bs-0424R; RRID: AB_10858058
Rabbit anti-STAT3	Bioss	Cat# bsm-52235R
Rabbit anti-pSTAT3	Bioss	Cat# bs-1658R;RRID: AB_10855117
Goat anti-rabbit IgG	Bioss	Cat# bs-0295G; RRID: AB_10856483
Rabbit anti-mIL6R	Bioss	Cat# bs-23660R
Rabbit anti-MMP13	Bioss	Cat# bs-10250R
Rabbit anti-IL6ST	BioLegend	Cat# 149401; RRID: AB_2565294
Rabbit anti-mIL6R	BioLegend	Cat# 115803; RRID: AB_313674
Rabbit anti-IL1RⅡ	Abcam	Cat# ab212208
Mouse anti-TNFR1	Abcam	Cat# ab194814; RRID: AB_2889242
Goat anti-rabbit IgG H&L (Alexa Fluor® 488)	Abcam	Cat# ab150077; RRID: AB_2630356
Goat anti-mouse IgG H&L (Alexa Fluor® 488)	Abcam	Cat# ab150113; RRID: AB_2576208
Rabbit anti-CD81	Abcam	Cat# ab109201; RRID: AB_10866464
Rabbit anti-CD9	Abcam	Cat# ab307085
Rabbit anti-TSG101	Abcam	Cat# ab125011; RRID: AB_10974262
Rabbit anti-HSP27	Abcam	Cat# ab12351; RRID: AB_299035
Rabbit anti-β Tubulin	Abcam	Cat# ab6046; RRID: AB_2210370
Rabbit anti-TNFR1	Abcam	Cat# ab223352
Rabbit anti-IL1RⅡ	Abcam	Cat# ab273025
Biological samples
Primary mouse chondrocytes	C57BL/6 mice in this study	N/A
Mouse bone marrow macrophages	C57BL/6 mice in this study	N/A
Chemicals, peptides, and recombinant proteins
Collagenase D	Roche	Cat# roche.11088858001
Fetal bovine serum	Hyclone	Cat# SH30406.02
Recombinant mouse M-CSF	R&D Systems	Cat# 416-ML-050/CF
Recombinant mouse RANKL	R&D Systems	Cat# 462-TR-010/CF
Recombinant human TNFα	R&D Systems	Cat# 210-TA-020
Recombinant human IL1β	Sigma-Aldrichs	Cat# SRP3083
Recombinant human gp130Fc	R&D Systems	Cat# 671-GP-100
Recombinant mouse gp130Fc	R&D Systems	Cat# 468-MG-100
Recombinant mouse hyper IL6	R&D Systems	Cat# 9038-SR-025
Penicillin-streptomycin	Hyclone	Cat# SV30010
Complete Freund’s Adjuvant	Chondrex	Cat# 7001
Incomplete Freund’s Adjuvant	Chondrex	Cat# 7002
Chicken collagen-II	Chondrex	Cat# 20011
RIPA buffer	Thermo-Scientific	Cat# 89901
Paraformaldehyde	Servicebio	G1101
EDTA	Servicebio	G1105
Safranin O-Fast Green staining solution	Servicebio	G1053
EV-depleted FBS	System Biosciences	Cat# EXO-FBS-250A-1
Critical commercial assays
QUANTI-Blue™ Solution	InvivoGen	rep-qbs
TRAP stain kit	Sigma-Aldrich	Cat# SCR004
BCA assay kit	Thermo Fisher	Cat# 23225
Mouse Luminex Discovery Assay kit	R&D Systems	Cat# LXSAMSM
Exostep™ kit	Immunostep	Cat# ExoS-25-C9
BD Quantibrite ™ Beads PE Fluorescence Quantitation Kit	BD	Cat# 340495
Deposited data
Mouse primary chondrocytes RNA expression dataset	Liu et al.16	Table S2
Experimental models: Cell lines
HEK293T cells	ATCC	CRL-3216; RRID: CVCL_0063
HEK-Blue™ IL6 Reporter cells	InvivoGen	hkb-hil6; RRID: CVCL_UF60
HEK-Blue™ TNFα Reporter cells	InvivoGen	hkb-tnfdmyd; RRID: CVCL_UF25
HEK-Blue™ IL1β Reporter cells	InvivoGen	hkb-il1bv2; RRID: CVCL_A8CL
Experimental models: Organisms/strains
C57BL/6 mice	Laboratory Animal Center of TMMU	this manuscript
BALB/c mice	Laboratory Animal Center of TMMU	this manuscript
DBA/1J mice	Laboratory Animal Center of TMMU	this manuscript
Col2a1-cre mice	Jackson Laboratories	RRID:IMSR_JAX:003554
il6stfl/fl mice	Cyagen Biosciences	S-CKO-03111
Oligonucleotides
Primer used, see Table S3	N/A	N/A
Recombinant DNA
IL6ST-eGFP-CD63	This Paper	N/A
IL6ST-mCherry-syntenin	This Paper	N/A
TNFR1-eGFP-CD63	This Paper	N/A
TNFR1-mCherry-syntenin	This Paper	N/A
IL1RⅡ-eGFP-CD63	This Paper	N/A
IL1RⅡ-mCherry-syntenin	This Paper	N/A
Software and algorithms
GraphPad Prism 9.4.0	GraphPad	http://www.graphpad-prism.cn/; RRID: SCR_002798
FlowJo v.10	Tree Star, Inc.	https://www.flowjo.com/; RRID: SCR_008520
AlphaFold2	DeepMind	https://github.com/deepmind/alphafold
Pymol v2.5	Schrödinger, Inc.	; RRID: SCR_000305
CT Analyser	Bruker	http://bruker-micro-ct-software/
ImageJ v1.54f	National Institutes of Health	https://imagej.net/; RRID: SCR_003070