Table 2. Top signaling pathways implicated by spatially upregulated genes that overlap between superficial and hypertrophic zones as well as intermediate/deep and resting zones.

Zones	Name	Ratio	P-value	Regulated Genes
SZ and HZ	Inhibition of Angiogenesisby TSP1	4/31 (13%)	1.58E-04	CD47,GUCY1A3,CD36,MMP9
	Hepatic Fibrosis/HepaticStellate Cell Activation	7/133 (5%)	1.70E-04	COL1A2,COL1A1,IGF1,MMP13, IGFBP5,SERPINE1,MMP9
	Atherosclerosis Signaling	6/111 (5%)	3.55E-04	COL1A2,COL1A1,CD36,MMP13, MMP9, TNFRSF12A
	Axonal Guidance Signaling	11/406 (3%)	7.41E-04	RAC2,GNG11,TUBB6,IGF1,ADAMTS1, ARHGEF1,MMP13,PRKCH, PLXND1,ABLIM1,MMP9
	ERK/MAPK Signaling	7/179 (4%)	9.55E-04	ETS1,RAC2,DUSP1,DUSP6, PPM1L,HSPB1,ELF1
	Natural Killer Cell Signaling	5/93 (5%)	1.45E-03	RAC2,TYROBP,FCER1G,PRKCH, INPP5D
	LXR/RXR Activation	5/107 (5%)	2.29E-03	CD36,ABCG1,PLTP,MMP9, ABCA1
	Guanosine NucleotidesDegradation III	2/12 (17%)	4.90E-03	GDA,PNP
	Xanthine and Xanthosine Salvage	1/1 (100%)	8.91E-03	PNP
	Dendritic Cell Maturation	5/155 (3%)	9.77E-03	B2M,COL1A2,COL1A1,TYROBP, FCER1G
IDZ and RZ	Glutamate Receptor Signaling	3/59 (5%)	8.71E-04	GLS,SLC1A1,GRIA3
	Role of Osteoblasts,Osteoclasts and Chondrocytesin Rheumatoid Arthritis	4/215 (2%)	6.03E-03	FRZB,BMP3,SFRP5,SFRP1
	Asparagine Degradation I	1/2 (50%)	6.92E-03	ASRGL1
	Glutamine Degradation I	1/2 (50%)	6.92E-03	GLS
	Heparan SulfateBiosynthesis (Late Stages)	2/43 (5%)	9.77E-03	CHST11,EXTL1
	Heparan SulfateBiosynthesis	2/50 (4%)	1.32E-02	CHST11,EXTL1
	Glycogen Biosynthesis II(from UDP-D-Glucose)	1/5 (20%)	1.74E-02	GYS1
	Wnt/β-cateninSignaling	3/158 (2%)	1.78E-02	FRZB,SFRP5,SFRP1
	Basal Cell CarcinomaSignaling	2/66 (3%)	2.14E-02	GLI2,BMP3
	BMP signaling pathway	2/74 (3%)	2.63E-02	BMP3,GREM1

*SZ, superficial zone; IDZ, intermediate/deep zone; RZ, resting zone; HZ, hypertrophic zone.