MicroRNA

MicroRNA Overview
Small non-coding ssRNA (~22nts) that negatively
regulate gene expression by binding to 3-UTR region
and inhibiting translation or inducing degradation of
mRNA
Involved in the fine tuning of many processes including
cell proliferation, differentiation, and cell death.
Play important role in pathogenesis of several human
diseases.

MicroRNA-210
Upregulated in response to hypoxia induces
angiogenesis
Overexpression stimulates formation of capillary-like
structures in vitro in normoxic conditions and VEGFdriven cell migration
Several studies out of Japan have demonstrated that
direct administration of synthetic MicroRNA-210 can
enhance the healing of the ACL, Meniscus, and Achilles
tendon via upregulation of VEGF, bFGF, and Collagen

Effect on Ligament Healing

Hypothesized that miRNA-210 administration would
augment healing of the ACL after partial transection by
accelerating angiogenesis.

Shoji T, Nakasa T, Yamasaki K, et al. The effect of intra-articular injection of microRNA-210 on ligament
healing in a rat model.

Effect on Ligament Healing

1. Temporal expression pattern of miR-210 after partial
transection of the ACL:
Initial downregulation soon after injury
with gradual upregulation thereafter
3x increase between Day 0 and Week 4

Shoji T, Nakasa T, Yamasaki K, et al. The effect of intra-articular injection of microRNA-210 on ligament
healing in a rat model.

Effect on Ligament Healing

2. Effect of intra-articular injection of miR-210 on ligament healing after

partial transection of the ACL:

-injected 30uL miR210-Atelocollagen complex (20ug/15uL) directly into the knee
joint immediately after transection

3. Results:
miR-210, VEGF, FGF2, COL1 Expression
# of blood vessels
ultimate load to failure at 4 weeks

Shoji T, Nakasa T, Yamasaki K, et al. The effect of intra-articular injection of microRNA-210 on ligament
healing in a rat model.

Effect on Ligament Healing

3. Results:
miR-210, VEGF, FGF2, COL1 Expression
# of blood vessels

Shoji T, Nakasa T, Yamasaki K, et al. The effect of intra-articular injection of microRNA-210 on

ligament healing in a rat model.

Effect on Ligament Healing

3. Results:
miR-210, VEGF, FGF2, COL1 Expression
# of blood vessels
ultimate load to failure at 4 weeks
- 30.5 3.1 N vs 22.8 3.1 N

Shoji T, Nakasa T, Yamasaki K, et al. The effect of intra-articular injection of microRNA-210 on ligament
healing in a rat model.

Effect on Ligament Healing

3. Results:

miR-210, VEGF, FGF2, COL1 Expression

# of blood vessels
ultimate load to failure at 4 weeks
Histology:

Shoji T, Nakasa T, Yamasaki K, et al. The effect of intra-articular injection of microRNA-210 on

ligament healing in a rat model.

Meniscal Healing
In vitro
VEGF, FGF2 production by synovial cells
COL2a1 expression by meniscal cells

In Vivo
4 weeks: Defect was filled and repaired; Increase in # of blood
vessels
12 weeks: Injured site was healed and less articular cartilage
degeneration

Kawanishi Y, Nakasa T, Shoji T, et al. Intra-articular injection of synthetic microRNA-210 accelerates

avascular meniscal

Achilles Tendon Healing

Completely transected and repaired Achilles tendons
followed by injection of ds microRNA-210
Regular, dense collagen with a larger fiber diameter at 2 & 6
weeks
Parallel/dense fibers vs wavy/loose at 12 weeks
VEGF, FGF2, COL1 Expression at 2 weeks
ultimate load to failure at 2 weeks
Abundant Vessels at 2 weeks, no significant difference at 6
weeks
Usman MA, Nakasa T, Shoji T, et al. The effect of administration of double stranded MicroRNA-210 on
acceleration of Achilles tendon healing in a rat model. J Orthop Sci. 2015;20(3):538-46..

miRNA-210 coated UHMW Scaffold

Studies
Augmentation of ligament healing via MicroRNA coated
UHMW PCL scaffold
Providing structural integrity while allowing for a targeted, controlled,
and sustained delivery of MicroRNA