Hyaluronic Acid Incorporation into Scaffolds for Bone and Cartilage Regeneration - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 22

(ECM) makes articular cartilage a biphasic tissue that plays a vital
part in the load-bearing capacity of joints.
One of the key components of the ECM of articular cartilage is HA, a
non-sulfated glycosaminoglycan (GAG) composed of repeating units
of d -glucuronic acid and N -acetyl- d -glucosamine [4-7]. HA acts as
the anchor for sulfated GAG within the ECM, such as chondroitin
sulfate (CS), forming larger molecules called aggrecans [6, 7]. The
highly negatively-charged aggrecans trap water within their network
and are responsible for the resilience of cartilage. HA is also a major
contributor to the functionality and hydrodynamics of the synovial
fluid and stimulates chondrocyte proliferation and migration [3,
8, 9]. It interacts with chondrocytes via surface receptors, such as
CD44, leading to the activation of a sophisticated pathway which
helps to retain their phenotype [10-13]. HA also plays a crucial role
in cartilage development as it is differentially regulated during limb
bud formation and mesenchymal cell condensation [14].
On the other hand, HA is a minor component in the structural matrix
of bone, but it is still involved in bone biology [15]. Endogenous
HA seems to play a role in bone resorption [16] whereas exogenous
HA has been shown to be osteoinductive [17]. HA can be produced
by osteoblasts [18, 19] and osteoclasts [20, 21] and has been found
in the cytoplasm of osteoprogenitor cells [22]. CD44 is expressed
by osteoclasts and to a small extent by osteoblasts [23]. HA can
further bind hydroxyapatite, without affecting mineral growth
[24], and the levels of HA are altered in certain bone diseases,
such as osteogenesis imperfecta [25]. HA plays a major role in the
endochondral ossification of the growth plate, where HA is found
in higher concentrations in the hypertrophic zone [22, 26, 27].
Correct production of HA in the growth plate is critical for bone
development, as shown by several knockout models [28, 29]. Also
of interest in bone repair, HA is found in high concentrations in the
early fracture callus [30].