What’s New in Musculoskeletal Basic Science 2019

Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all such OrthoBuzz summaries. This month, co-author Philipp B. Leucht, MD selected the most clinically compelling findings from the 40 studies summarized in the December 4, 2019 “What’s New in Musculoskeletal Basic Science.”

Muscle Regeneration
–Recent findings about the cellular players in muscle regeneration may allow further development of clinical treatment options for patients with muscle sprains, tears, and loss. Toward that end, Wosczyna et al. established the crucial role of fibroadipogenic progenitors (FAPs, also called mesenchymal stromal cells) in muscle repair and maintenance.¹ Using a mouse model, the researchers showed that FAPs are necessary for muscle regeneration by supporting muscle stem cells.

Bone-Brain Crosstalk
–The bone-derived hormone osteocalcin supports development of the musculoskeletal system and the brain. Osteocalcin can regulate anxiety and cognition in adult mice, and Obri et al. postulated that declining levels of osteocalcin may be responsible for the cognitive decline seen in aging.² This finding may spur investigations into exogenous treatment with osteocalcin to restore brain function.

Tendon Regeneration
–Tendon cells express the transcription factor Scleraxis, which has facilitated the identification of the tendon stem progenitor cell (TSPC). Best and Loiselle identified a Scleraxis-positive cell population in the bridging scar tissue after tendon injury.³ These findings suggest that TSPCs are present in the adult tendon and contribute to the healing response; however, their small number does not result in successful tendon regeneration, but rather in scar formation with interspersed tendon tissue.

–Abraham et al. identified the upregulation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and its downstream targets in tendinopathy-affected human rotator cuff tendons.⁴ Using a transgenic mouse model in which IKKß (inhibitor of nuclear factor kappa-B kinase subunit beta), a key regulator of inflammation, was overexpressed, they demonstrated the development of tendinopathy in mouse rotator cuff tendons. The deletion of IKKß had a protective effect from chronic overuse.

Bone Regeneration
–Successful bone healing after fracture is highly dependent on the presence and activation of skeletal stem cells. Chan et al. precisely defined the human skeletal stem cell (hSSC), demonstrated the hSSC’s role in human fracture repair, and provided evidence that these cells generate a bone marrow-supportive niche.⁵ These cells also give rise to bone, cartilage, and stromal progenitor cells.

References

1. Wosczyna MN, Konishi CT, Perez Carbajal EE, Wang TT, Walsh RA, Gan Q, Wagner MW, Rando TA. Mesenchymal stromal cells are required for regeneration and homeostatic maintenance of skeletal muscle. Cell Rep.2019 May 14;27(7):2029-2035.e5.
2. Obri A, Khrimian L, Karsenty G, Oury F. Osteocalcin in the brain: from embryonic development to age-related decline in cognition. Nat Rev Endocrinol.2018 Mar;14(3):174-82. Epub 2018 Jan 29.
3. Best KT, Loiselle AE. Scleraxis lineage cells contribute to organized bridging tissue during tendon healing and identify a subpopulation of resident tendon cells. FASEB J.2019 Jul;33(7):8578-87. Epub 2019 Apr 5.
4. Abraham AC, Shah SA, Golman M, Song L, Li X, Kurtaliaj I, Akbar M, Millar NL, Abu-Amer Y, Galatz LM, Thomopoulos S. Targeting the NF-κB signaling pathway in chronic tendon disease. Sci Transl Med.2019 Feb 27;11(481):eaav4319.
5. Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT. Identification of the human skeletal stem cell. 2018; Sep 20;175(1):43-56.e21.