https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60243-2.pdf

Osteoarthritis: an update with relevance for clinical practice

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(12)00115-1.pdf

Recent advances in bone tissue engineering scaffolds.

https://www.oarsijournal.com/article/S1063-4584(10)00238-4/pdf

The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the mouse

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(09)00015-8.pdf

Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF).

The extracellular matrix (ECM), and especially the connective tissue with its collagen, links tissues of the body together and plays an important role in the force transmission and tissue structure maintenance especially in tendons, ligaments, bone, and muscle. The ECM turnover is influenced by physical activity, and both collagen synthesis and degrading metalloprotease enzymes increase with mechanical loading. Both transcription and posttranslational modifications, as well as local and systemic release of growth factors, are enhanced following exercise. For tendons, metabolic activity, circulatory responses, and collagen turnover are demonstrated to be more pronounced in humans than hitherto thought. Conversely, inactivity markedly decreases collagen turnover in both tendon and muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as, dependent on the type of collagen in question, some degree of net collagen synthesis. These changes will modify the mechanical properties and the viscoelastic characteristics of the tissue, decrease its stress, and likely make it more load resistant. Cross-linking in connective tissue involves an intimate, enzymatical interplay between collagen synthesis and ECM proteoglycan components during growth and maturation and influences the collagen-derived functional properties of the tissue. With aging, glycation contributes to additional cross-linking which modifies tissue stiffness. Physiological signaling pathways from mechanical loading to changes in ECM most likely involve feedback signaling that results in rapid alterations in the mechanical properties of the ECM. In developing skeletal muscle, an important interplay between muscle cells and the ECM is present, and some evidence from adult human muscle suggests common signaling pathways to stimulate contractile and ECM components. Unaccostumed overloading responses suggest an important role of ECM in the adaptation of myofibrillar structures in adult muscle. Development of overuse injury in tendons involve morphological and biochemical changes including altered collagen typing and fibril size, hypervascularization zones, accumulation of nociceptive substances, and impaired collagen degradation activity. Counteracting these phenomena requires adjusted loading rather than absence of loading in the form of immobilization. Full understanding of these physiological processes will provide the physiological basis for understanding of tissue overloading and injury seen in both tendons and muscle with repetitive work and leisure time physical activity.

Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading

Fibrin/hyaluronic acid hydrogel for combined delivery of gapmers and chondrocytes as a gene therapy approach for osteoarthritis

The dog as a spontaneous animal model for human intervertebral disc degeneration

Background Mechanical and inflammatory processes add to osteoarthritis (OA). To what extent both processes contribute during the onset of OA after a cartilage trauma is unknown. This study evaluates whether local cartilage damage leads to focally confined or more generalized cartilage damage with synovial inflammation in the early development of joint tissue degeneration. Methods In nine goats, cartilage damage was surgically induced on the weight bearing area of exclusively the medial femoral condyle of the right knee joint. The other tibio-femoral compartments, lateral femoral condyle and lateral medial tibial plateau, were left untouched. The contralateral left knee joint of each animal served as an intra-animal control. Twenty weeks post-surgery changes in cartilage matrix integrity in each of the four compartments, medial and lateral synovial tissue inflammation, and synovial fluid IL-1β and TNFα were evaluated. Results In the experimental medial femoral plateau, significant macroscopic, histologic, and biochemical cartilage damage was observed versus the contralateral control compartments. Also the articulating cartilage of the experimental medial tibial plateau was significantly more damaged. Whereas, no differences were seen between the lateral compartments of experimental and contralateral control joints. Synovial tissue inflammation was mild and only macroscopically (not histologically) significantly increased in the experimental medial compartments. Synovial fluid IL-1β level was not different between experimental and contralateral control joints, and TNFα was overall beneath the detection limit. Conclusions Local cartilage damage is a trigger for development of OA, which in early onset seems primarily mechanically driven. Early treatment of traumatic cartilage damage should take this mechanical component into consideration.

Early evolving joint degeneration by cartilage trauma is primarily mechanically controlled.

Background: Cartilage defects result in joint inflammation. The presence of proinflammatory factors has been described to negatively affect cartilage formation. Purpose: To evaluate the effect and timing of administration of triamcinolone acetonide (TAA), an anti-inflammatory drug, on cartilage repair using a mouse model. Study Design: Controlled laboratory study. Methods: A full-thickness cartilage defect was created in the trochlear groove of 10-week-old male DBA/1 mice (N = 80). Mice received an intra-articular injection of TAA or saline on day 1 or 7 after induction of the defect. Mice were euthanized on days 10 and 28 for histological evaluation of cartilage defect repair, synovial inflammation, and synovial membrane thickness. Results: Mice injected with TAA had significantly less synovial inflammation at day 10 than saline-injected mice independent of the time of administration. At day 28, the levels of synovitis dropped toward healthy levels; nevertheless, the synovial membrane was thinner in TAA- than in saline-injected mice, reaching statistical significance in animals injected on day 1 (70.1 ± 31.9 µm vs 111.9 ± 30.9 µm, respectively; P = .01) but not in animals injected on day 7 (68.2 ± 21.86 µm vs 90.2 ± 21.29 µm, respectively; P = .26). A thinner synovial membrane was moderately associated with less filling of the defect after 10 and 28 days (r = 0.42, P = .02; r = 0.47, P = .01, respectively). Whereas 10 days after surgery there was no difference in the area of the defect filled and the cell density in the defect area between saline- and TAA-injected knees, filling of the defect at day 28 was lower in TAA- than in saline-injected knees for both injection time points (day 1 injection, P = .04; day 7 injection, P = .01). Moreover, there was less collagen type 2 staining in the filled defect area in TAA- than in saline-injected knees after 28 days, reaching statistical significance in day 1–injected knees (2.6% vs 18.5%, respectively; P = .01) but not in day 7–injected knees (7.4% vs 15.8%, respectively; P = .27). Conclusion: Intra-articular injection of TAA reduced synovial inflammation but negatively affected cartilage repair. This implies that inhibition of inflammation may inhibit cartilage repair or that TAA has a direct negative effect on cartilage formation. Clinical Relevance: Our findings show that TAA can inhibit cartilage defect repair. Therefore, we suggest not using TAA to reduce inflammation in a cartilage repair setting.

https://journals.sagepub.com/doi/pdf/10.1177/03635465221083693

Intra-articular Administration of Triamcinolone Acetonide in a Murine Cartilage Defect Model Reduces Inflammation but Inhibits Endogenous Cartilage Repair

Regenerated cartilage formed after Autologous Chondrocyte Implantation may be of suboptimal quality due to postulated hypertrophic changes. Parathyroid hormone-related peptide, containing the parathyroid hormone sequence (PTHrP 1-34), enhances cartilage growth during development and inhibits hypertrophic differentiation of mesenchymal stromal cells (MSCs) and growth plate chondrocytes. This study aims to determine the possible anabolic and/or hypertrophic effect of PTH on human articular chondrocytes. Healthy human articular cartilage-derived chondrocytes (n = 6 donors) were cultured on type II collagen-coated transwells with/without 0.1 or 1.0 μM PTH from day 0, 9, or 21 until the end of culture (day 28). Extracellular matrix production, (pre)hypertrophy and PTH signaling were assessed by RT-qPCR and/or immunohistochemistry for collagen type I, II, X, RUNX2, MMP13, PTHR1 and IHH and by determining glycosaminoglycan production and DNA content. The Bern score assessed cartilage quality by histology. Regardless of the concentration and initiation of supplementation, PTH treatment significantly decreased DNA and glycosaminoglycan content and reduced the Bern score compared with controls. Type I collagen deposition was increased, whereas PTHR1 expression and type II collagen deposition were decreased by PTH supplementation. Expression of the (pre)hypertrophic markers MMP13, RUNX2, IHH and type X collagen were not affected by PTH. In conclusion, PTH supplementation to healthy human articular chondrocytes did not affect hypertrophic differentiation, but negatively influenced cartilage quality, the tissues' extracellular matrix and cell content. Although PTH may be an effective inhibitor of hypertrophic differentiation in MSC-based cartilage repair, care may be warranted in applying accessory PTH treatment due to its effects on articular chondrocytes.

/pdf/pth-decreases-in-vitro-human-cartilage-regeneration-without-1fljirxy1x.pdf

Laura B. Creemers

Papers

Fibrin/hyaluronic acid hydrogel for combined delivery of gapmers and chondrocytes as a gene therapy approach for osteoarthritis

The dog as a spontaneous animal model for human intervertebral disc degeneration

Early evolving joint degeneration by cartilage trauma is primarily mechanically controlled.

Intra-articular Administration of Triamcinolone Acetonide in a Murine Cartilage Defect Model Reduces Inflammation but Inhibits Endogenous Cartilage Repair

PTH decreases in vitro human cartilage regeneration without affecting hypertrophic differentiation.