Fig. 1 Crosstalk between tissues beyond cartilage and bone may provide insight and clarity into joint disease onset and progression.
Courtesy of Megan L. Killian, PhD

AAOS Now

Published 9/1/2016
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Terry Stanton; Thomas P. Vail, MD; Tamara Alliston, PhD

Bone and Cartilage: Interpreting the Crosstalk

AAOS/ORS Research Symposium examines interaction between joint tissues
In electronics, "crosstalk" is the usually undesirable effect of a signal in one channel on another circuit or channel. In orthopaedic research, crosstalk can refer to interactions among tissues, particularly with respect to the onset and development of joint diseases. This crosstalk normally allows the healthy joint to seamlessly integrate the mechanical and biological functions of multiple tissues, including cartilage, bone, synovium, nerve, vasculature, and others, to support smooth, pain-free movement. Understanding this crosstalk and the joint as an integrated whole, rather than the sum of its parts, is essential for identifying mechanisms of joint disease.

Despite advances in understanding individual joint tissues, surprisingly little is known about the crosstalk among these tissues that instigates joint disease. More basic science research in this area is needed to improve the ability of orthopaedic surgeons to diagnose and treat musculoskeletal conditions. To address this critical knowledge gap, the AAOS and the Orthopaedic Research Society (ORS) chose joint crosstalk as the topic for their 2016 annual Research Symposium.

The Tackling Joint Disease by Understanding Crosstalk between Cartilage and Bone Research Symposium provided a unique forum for experts on bone, cartilage, and other tissues to consider the integrated function of joint tissues across the lifespan. It brought together researchers from a variety of disciplines, including orthopaedic surgeons, rheumatologists, engineers, and biologists. To advance understanding of normal joint function, degeneration, and healing, the symposium had the following goals:

  • define the knowledge base for crosstalk among cells and tissues of the joint
  • identify gaps in knowledge and research priorities
  • inspire collaboration among researchers with distinct disciplinary and tissue expertise
  • cultivate and educate a diverse cohort of new investigators to address novel research challenges

Each of the sessions featured one or more crosstalk mechanisms, including nerve, vascular, synovial, and immune contributions, as well as growth factors, hypoxia, and physical factors. Speakers with expertise in joint pain, the microbiome, and genomics contributed diverse and novel perspectives. Each session concluded with a lively 30-minute discussion about unresolved questions that helped to identify the leading edge of the field and future research priorities. Equally valuable were the informal interactions at the poster sessions that sparked new ideas and engaged new investigators. Following are some of the key highlights of the meeting.

Bone and cartilage crosstalk
Bone and cartilage function at a level well beyond the mechanical interaction, with evidence of cellular signaling among multiple cell types across the subchondral plate. This insight clarifies the significance of bone marrow lesions and their utility in analyzing the progression of joint disease with advanced imaging. Understanding these mechanisms will lead to an improved understanding of joint pain. 

Joint crosstalk beyond bone and cartilage
Although osteoarthritis (OA) is traditionally defined as the degradation of joint cartilage and subchondral bone that results in joint space narrowing, pain, and disuse, the paradigm of OA as simply a disease of articular cartilage is no longer upheld. This session provoked discussion on the joint "organ" in which dysfunction affects not just articular cartilage and subchondral bone, but also the synovium, synovial fluid, intra-articular ligaments and tendons, tendon-bone connective tissues (entheses), surrounding musculature, fat pads, and more (Fig. 1). Multiple systemic and mechanical factors affect these complex systems. For example, immunologic and metabolic changes associated with diabetes, obesity, and aging participate in this crosstalk and suggest new opportunities for therapies.

Mechanobiology in joint crosstalk
Exogenous and intrinsic forces act at multiple length scales in the joint to affect skeletal cell function, solute transport, and the material quality of joint tissues. Several speakers talked about the central role of transforming growth factor-beta (TGFβ) in joint homeostasis and disease, and how the activity of this pathway is regulated at multiple levels by physical cues. Exciting new molecular mechanisms suggest opportunities to more precisely intervene in these signaling pathways to restore homeostasis and limit disease progression. 

Crosstalk at the vascular interface
Crosstalk at the physical and molecular interface of vascular and avascular tissues depends on permeability of subchondral bone and proper regulation of cellular function in the context of hypoxia. New tissue engineering strategies hold promise to restore skeletal vascularity and reverse some of the pathologic features of skeletal disease.

Broad concepts
Use of large clinical and experimental data sets is reshaping our approach to understanding the mechanisms that operate in the joint and those that predispose individuals for joint disease or promote superior cartilage repair. Incorporating advances in genomic analysis and in the exploration of the role of the microbiome will be pivotal for unraveling the mechanisms that drive joint disease. Insights on joint crosstalk will also inform development of new approaches, targeting one or more joint tissues, to overcome current limitations in the diagnosis and treatment of joint disease.

On the horizon
Given the urgent demand for improved clinical solutions and the recent advances in bone and cartilage research, this symposium was valuable for stimulating the dialogue to accelerate research on crosstalk among tissues in the joint. Such research can lead to understanding and ultimately treating degenerative joint disease. To that end, future research directions identified at the symposium will be incorporated into the AAOS Unified Research Agenda, which communicates musculoskeletal research needs to funding agencies, Congress, and the public. For additional information, visit the symposium poster at the AAOS Annual Meeting or attend the Workshop on Joint Crosstalk at the ORS Annual Meeting in San Diego in 2017.

The next AAOS/ORS research symposium, Translating Orthopaedic Technologies into Clinical Practice: Pathways from Novel Ideas to Improvements in Standard of Care is scheduled for May 2017. For more information, contact Erin Ransford, manager, research advocacy, at ransford@aaos.org

Terry Stanton is the senior science writer for AAOS Now. He can be reached at tstanton@aaos.org

Thomas P. Vail, MD, is James L. Young Professor and chairman, Department of Orthopaedic Surgery, University of California, San Francisco, where Tamara Alliston, PhD, is an associate professor.
Drs. Vail and Alliston cochaired the 2016 AAOS/ORS Research Symposium.