Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomédical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article. J Bone Joint Surg Am. 2012;94:2289-95 • http://dx.
Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event. We show that human and bovine primary NP cells express high levels of ANKH and ENPP1, and low or undetectable levels of TNAP. Bovine NPs transduced to express TNAP were capable of matrix mineralization, which was further enhanced by ANKH knockdown. TNF treatment or overexpression promoted a greater increase in mineralization of TNAP-expressing cells by downregulating the expression of ANKH and ENPP1 via NF-κB activation. The increased mineralization was accompanied by phenotypic changes that resemble chondrocyte hypertrophy, including increased RUNX2 and COL10A1 mRNA; mirroring the cellular alterations typical of samples from IDD patients. Disc organ explants injected with TNAP/TNF- or TNAP/shANKH-overexpressing cells showed increased mineral content inside the NP. Together, our results confirm interactions between TNF and downstream regulators of matrix mineralization in NP cells, providing evidence to suggest their participation in NP calcification during IDD.
Developments in several fields, including molecular and stemcell biology, biomaterials, biomechanics, and molecular genetics, have all contributed to advancements in orthopaedic research this past year. Improvements and refinements in laboratory techniques have hastened the pace of progress in research. The primary challenge for the clinician is to stay abreast of advances in areas related to the biology and biomechanics of musculoskeletal tissues. In this review, we have attempted to highlight advances that have the most potential for early translation to clinical practice in the areas of tendon biology, spinal disc degeneration and regeneration, meniscus repair and regeneration, and cartilage degeneration and repair. Tendon Healing and Tendon Repair TendinosisUnderstanding the underlying mechanism(s) involved in degenerative tendinosis continues to be an important area in tendon research. Recent work has focused on the signaling mechanisms that lead to degenerative phenotypic changes in tendon, such as glycosaminoglycan (GAG) accumulation and ectopic calcification. Treadmill running has been used in small animal models to induce overuse changes in tendon. With use of these models, increased expression of heparin affinity regulatory peptide (HARP)/pleiotrophin and SOX-9 were seen, which are known to regulate chondrocyte formation and result in chondrocytic phenotypic changes 1 . The adverse effect of excessive GAG in tendon matrix was also demonstrated by the altered tendon biomechanical properties in a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) knockout mice. ADAMTS5 plays an important role in removing pericellular and interfibrillar aggrecan, which maintains normal collagen architecture and matrix organization 2 .
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