Table 1.

Summary of cytokines across all conditions.

Cytokines	Fold change from control (CI = 95%)						Role in OA
	SVF day 1	SVF day 3	SVF + adipo day 1	SVF + adipo day 3	MSC seeding	MSC media
Proinflammatory
MIF	0.94	0.93	0.89	0.99	1.49	0.79	Induce the release of proinflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, IL-6, and IL-8 [6] and MIF levels in synovial fluid correlate to OA severity [7]
TNF-β	1.00	1.26	1.03	1.28	1.52	1.18	TNF-beta stimulates cartilage matrix breakdown [8]
IL-1α	1.21	1.35	0.98	1.26	1.34	N.D.	Highly expressed in OA-derived human articular cartilage [9]
IL-1β	1.03	1.12	0.59	0.89	1.00	0.94	Induce inflammatory reactions and catabolic effects independently as well as in combination with other mediators in OA with respect to the articular cartilage [10]
IL-12	0.67	0.86	0.49	0.78	1.00	0.90	Expressed by infiltrating macrophages and synovial cells in OA [11]
IL-17	0.70	1.17	0.83	0.90	0.96	0.09	Inhibit the synthesis of proteoglycans in OA and upregulate catabolic enzymes which break down cartilage [10]
IFN-γ	0.96	0.86	0.89	0.80	0.99	0.93	Stimulate cartilage breakdown by production of enzymes via IL-1β [12]
Anti-inflammatory/dual role
IL-10	0.90	0.85	0.40	0.61	1.05	0.86	Expressed in chondrocytes and involved in collagen and aggrecan synthesis. Inhibition of catabolic enzymes and apoptosis of chondrocytes [10]
IL-2	0.81	2.35	0.69	0.74	1.23	1.35	Elevated levels are found in OA synovial fluid and increased levels correlate to increase severity [13]
IL-6	0.93	0.84	0.47	0.94	1.11	0.84	Catabolism aggrecan via aggrecanase activity [14] involved in the synthesis of tissue inhibitor of metalloproteinases known to stop cartilage breakdown [15]
Chemokines
GROα	1.02	0.89	0.79	0.87	0.94	1.12	Constitutively secreted by chondrocytes and secretion of this chemotactic protein is increased in stimulated osteoarthritic chondrocytes and synovial fibroblasts [16]
MIP-1β	0.92	0.83	0.86	1.17	1.16	1.14	Present in significantly higher levels in OA synovial fluid compared to normal synovial fluid [17]
RANTES	0.78	0.99	0.94	1.31	1.09	0.67	Secreted by IL-1 stimulated osteoarthritic chondrocytes and TNF-α stimulated synovial fibroblasts [16]
MCP-1	0.79	0.65	0.75	0.90	0.95	0.91	Constitutively expressed in osteoarthritic chondrocytes and increased secretion in IL-1 stimulated osteoarthritic chondrocytes [16]
MCP-3	0.83	1.07	0.82	0.95	0.97	N.D.	Activate immune cells such as monocytes, T lymphocytes, basophils, and eosinophils [18]
MIP-1α	0.83	0.67	0.82	0.90	1.04	0.95	Expressed by osteoarthritic derived chondrocytes and production is enhanced by TNF-α stimulated chondrocytes [19]
Growth factors
HGF	0.69	0.83	0.83	1.56	1.42	0.95	Promote osteophyte formation via MCP-1 mediated infiltration of immune cells into OA affected joint [20]
FGF-β	0.89	1.21	0.79	0.98	1.26	0.84	Potentiate articular cartilage resurfacing and may stimulate expression of MMP-13 [21, 22]
β-NGF	1.02	0.92	0.73	0.86	0.78	0.86	Higher expression is found in osteoarthritic derived chondrocyte compared to healthy chondrocytes [23]
GM-CSF	0.84	1.82	0.76	0.91	1.38	N.D.	Key mediator in inflammation and arthritic pain [24]
VEGF	0.71	0.82	0.51	0.71	1.00	0.84	Expressed in osteoarthritic-derived chondrocytes and shown to increase osteochondral angiogenesis in OA patients [25]
G-CSF	0.97	0.96	0.51	0.80	1.06	0.84	Can significantly increase nitrite levels in cartilage when combined with IL-1β explants [26]

A summary of cytokines across all the conditions treated with HA. The data is represented as fold change in concentration compared to control. A value more than one indicates the HA treatment increased the secretion of that cytokine in that condition. Bold values represent a significant fold change from control determined numerically using confidence interval set at 95%. Italic values were only detected in one of the three biological replicates for that condition.