Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Dec;3(1):22.
doi: 10.1186/s40634-016-0060-6. Epub 2016 Sep 13.

Basic science of osteoarthritis

Magali Cucchiarini  1 , Laura de Girolamo  2 , Giuseppe Filardo  3 , J Miguel Oliveira  4   5 , Patrick Orth  6   7 , Dietrich Pape  8   9 , Pascal Reboul  10
Affiliations

Basic science of osteoarthritis

Magali Cucchiarini et al. J Exp Orthop. 2016 Dec.

Abstract

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.

Keywords: Animal models; Articular cartilage; Bone; Interface; Osteoarthritis; Pathomechanisms; Stem cells; Tissue engineering.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
OA-associated changes in the human joint. Safranin O-stained histological sections from human normal versus OA knee joint cartilage are presented on the top panels. The lower panel is a representation of the different tissues implicated in the OA pathology with crosstalks
Fig. 2
Fig. 2
Factors regulating Wnt signaling in OA osteoblasts (modification from the original drawing representing the canonical Wnt route adapted from Baron & Kneissel 2013). APC, Adenomatous polyposis coli; DKK2, Dickkopf-related protein 2; DVL, Dishevelled protein; FZD, frizzled receptor; GSK3, glycogen synthase kinase 3; HGF, hepatocyte growth factor; LEF, lymphoid enhancing factor; LPR, lipoprotein receptor-related protein; R-Spo2, R-spondin 2; TCF, T-cell factor; TGF-β, transforming growth factor beta
Fig. 3
Fig. 3
Organization of the normal adult articular cartilage. a Organization of the chondrocytes in their ECM in superficial, middle, and deep zones. The cement line separates the calcified zone from the subchondral bone. Major ECM components are presented in the box. b Normal PCM and cell-matrix interface (adapted from Heinegård & Saxne 2011)
Fig. 4
Fig. 4
Pathological organization of OA cartilage. a Disrupted organization. b OA PCM and altered cell-matrix interface (adapted from Heinegård & Saxne 2011)
Fig. 5
Fig. 5
Cartilage homeostasis. Natural and pathological OA cellular and metabolic balance
Fig. 6
Fig. 6
Cell-matrix interface in OA. Interactions between membrane sensors/receptors at the surface of chondrocytes become altered during OA, leading to abnormal signalling and activation of OA-related pathways via integrins (a), syndecan-4 (b), DDR-2 (c), and CD44 (d)
Fig. 7
Fig. 7
Late sequela of a monocortical screw fixation. Left: caudal view on a cross-sectional area of the proximal tibial segment showing monocortical screw imprints of the tibial head. Right: Post-operative X-ray of the right sheep tibia shortly after an open wedge HTO in a foundering animal with a secondary dislocation of the tibial head (from Pape & Madry, 2013)
Fig. 8
Fig. 8
Plate design is crucial to meet the anatomical requirements of the sheep tibia. Proximally narrow, long and rigid plates (TomoFix small stature plate, Synthes, left) are advisable as opposed to anatomically shaped and broad plate designs (ContourLock, Arthrex, right) which fail to cover the sheep anatomy and may produce soft tissue impingement (from Pape & Madry, 2013)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aaron RK, Dyke JF, Ciombor DM, Ballon D, Lee J, Jung E, Tung GA. Perfusion abnormalities in subchondral bone associated with marrow edema, osteoarthritis, and avascular necrosis. Ann N Y Acad Sci. 2007;1117:124–137. doi: 10.1196/annals.1402.069. - DOI - PubMed
    1. Abed E, Chan TF, Delalandre A, Martel-Pelletier J, Pelletier JP, Lajeunesse D. R-spondins are newly recognized players in osteoarthritis that regulate Wnt signaling in osteoblasts. Arthritis Rheum. 2011;63(12):3865–3875. doi: 10.1002/art.30625. - DOI - PubMed
    1. Abed E, Couchourel D, Delalandre A, Duval N, Pelletier JP, Martel-Pelletier J, Lajeunesse D. Low sirtuin 1 levels in human osteoarthritis subchondral osteoblasts lead to abnormal sclerostin expression which decreases Wnt/β-catenin activity. Bone. 2014;59:28–36. doi: 10.1016/j.bone.2013.10.020. - DOI - PubMed
    1. Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, Toda K. Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc. 2006;14(12):1307–1314. doi: 10.1007/s00167-006-0124-8. - DOI - PubMed
    1. Allen M, Houlton J, Adams S, Rushton N. The surgical anatomy of the stifle joint in sheep. Vet Surg. 1998;27(6):596–605. doi: 10.1111/j.1532-950X.1998.tb00536.x. - DOI - PubMed

LinkOut - more resources